CMOS sensors for fluorescence lifetime imaging

Henderson, Robert K.; Rae, Bruce R.; Li, David

doi:10.1016/b978-0-08-102434-8.00012-x

Cited by 5 publications

(5 citation statements)

References 85 publications

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“…An emerging alternative to aforementioned intensifier based systems are Single Photon Avalanche Diode (SPAD) arrays manufactured with complementary-metal-oxide semiconductor (CMOS) technology 24 , which can operate with TCSPC [25][26][27][28][29][30][31] or time-gated [32][33][34][35][36][37] acquisition mode. The main advantages of SPAD arrays over conventional CCD/CMOS cameras are the picosecond temporal resolution, and single-photon sensitivity 38 , which make them ideal for a broad range of applications in the area of ultrafast time-resolved imaging 39 . Until recently, SPAD arrays had a relatively limited number of 'active areas' (or 'pixels') due to the physical constraints imposed by the need to fit complex timing electronics for each individual pixel on the same chip.…”

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confidence: 99%

Fluorescence lifetime imaging with a megapixel SPAD camera and neural network lifetime estimation

Žičkus

Morimoto

et al. 2020

Sci Rep

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Fluorescence lifetime imaging microscopy (FLIM) is a key technology that provides direct insight into cell metabolism, cell dynamics and protein activity. However, determining the lifetimes of different fluorescent proteins requires the detection of a relatively large number of photons, hence slowing down total acquisition times. Moreover, there are many cases, for example in studies of cell collectives, where wide-field imaging is desired. We report scan-less wide-field FLIM based on a 0.5 MP resolution, time-gated Single Photon Avalanche Diode (SPAD) camera, with acquisition rates up to 1 Hz. Fluorescence lifetime estimation is performed via a pre-trained artificial neural network with 1000-fold improvement in processing times compared to standard least squares fitting techniques. We utilised our system to image HT1080—human fibrosarcoma cell line as well as Convallaria. The results show promise for real-time FLIM and a viable route towards multi-megapixel fluorescence lifetime images, with a proof-of-principle mosaic image shown with 3.6 MP.

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Fluorescence lifetime imaging with a megapixel SPAD camera and neural network lifetime estimation

Žičkus

Morimoto

et al. 2020

Sci Rep

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“…To improve the efficiency of time-resolved luminescence imaging, area-array detectors were developed to achieve widefield time-resolved luminescence imaging of all the pixels (Urayama et al, 2003;Connally et al, 2006;Sun et al, 2009;Gahlaut and Miller, 2010;Li et al, 2010;Guo and Sonkusale, 2012;Hirvonen et al, 2014;Chen et al, 2015;Kuijk, 2015, 2016;Chen T. et al, 2017;Ulku et al, 2019;Henderson et al, 2020;Liu et al, 2020). A common CCD or CMOS sensor is composed of an area-array of photosensitive silicon diodes, each of which could sense photons in microseconds (Henderson et al, 2020), but the actual frame rate is probably no more than hundreds of frames per second due to the limitation of readout time.…”

Section: Overview Of Time-resolved Techniquesmentioning

confidence: 99%

“…To improve the efficiency of time-resolved luminescence imaging, area-array detectors were developed to achieve wide-field time-resolved luminescence imaging of all the pixels (Urayama et al, 2003 ; Connally et al, 2006 ; Sun et al, 2009 ; Gahlaut and Miller, 2010 ; Li et al, 2010 ; Guo and Sonkusale, 2012 ; Hirvonen et al, 2014 ; Chen et al, 2015 ; Ingelberts and Kuijk, 2015 , 2016 ; Chen T. et al, 2017 ; Ulku et al, 2019 ; Henderson et al, 2020 ; Liu et al, 2020 ). A common CCD or CMOS sensor is composed of an area-array of photosensitive silicon diodes, each of which could sense photons in microseconds (Henderson et al, 2020 ), but the actual frame rate is probably no more than hundreds of frames per second due to the limitation of readout time. To achieve both high gain and nanosecond resolution, micro channel plate (MCP) is developed and serves as a high-speed electronic shutter in the intensified cameras, which are widely used in wide-field time-gated imaging (Urayama et al, 2003 ; Connally et al, 2006 ; Sun et al, 2009 ; Gahlaut and Miller, 2010 ; Hirvonen et al, 2014 ; Chen T. et al, 2017 ; Liu et al, 2020 ).…”

Section: Overview Of Time-resolved Techniquesmentioning

confidence: 99%

“…But these high-speed cameras are very expensive. In order to image the luminescence lifetime globally, some labs developed a variety of novel CMOS cameras (Henderson et al, 2020 ), which could implement time-gated control (Ingelberts and Kuijk, 2015 , 2016 ), phase recording (Guo and Sonkusale, 2012 ; Chen et al, 2015 ; Ulku et al, 2019 ) or TCSPC (Li et al, 2010 ) on their sensor chips. Although these cameras could obtain luminescence lifetime images much faster than the scanning imaging, some of them were limited to detect mono or double exponential luminescence decay.…”

Section: Overview Of Time-resolved Techniquesmentioning

confidence: 99%

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Auto-Phase-Locked Time-Resolved Luminescence Detection: Principles, Applications, and Prospects

2020

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Time-resolved luminescence measurement is a useful technique which can eliminate the background signals from scattering and short-lived autofluorescence. However, the relative instruments always require pulsed excitation sources and high-speed detectors. Moreover, the excitation and detecting shutter should be precisely synchronized by electronic phase matching circuitry, leading to expensiveness and high-complexity. To make time-resolved luminescence instruments simple and cheap, the automatic synchronization method was developed by using a mechanical chopper acted as both of the pulse generator and detection shutter. Therefore, the excitation and detection can be synchronized and locked automatically as the optical paths fixed. In this paper, we first introduced the time-resolved luminescence measurements and review the progress and current state of this field. Then, we discussed low-cost time-resolved techniques, especially chopper-based time-resolved luminescence detections. After that, we focused on auto-phase-locked method and some of its meaningful applications, such as time-gated luminescence imaging, spectrometer, and luminescence lifetime detection. Finally, we concluded with a brief outlook for auto-phase-locked time-resolved luminescence detection systems.

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“…An emerging alternative to aforementioned intensifier based systems are Single Photon Avalanche Diode (SPAD) arrays manufactured with complementary-metal-oxide semiconductor (CMOS) technology [25], which can operate with TCSPC or time-gated acquisition mode. The main advantages of SPAD arrays over conventional CCD/CMOS cameras are the picosecond temporal resolution, and singlephoton sensitivity [26], which make them ideal for a broad range of applications in the area of ultrafast timeresolved imaging [27]. Until recently, SPAD arrays had a relatively limited number of 'active areas' (or 'pixels') due to the physical constraints imposed by the need to fit complex timing electronics for each individual pixel on the same chip.…”

mentioning

confidence: 99%

Wide-field Fluorescence Lifetime Imaging Microscopy with a High-Speed Mega-pixel SPAD Camera

Žičkus

Morimoto

et al. 2020

Preprint

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Fluorescence lifetime imaging microscopy (FLIM) is a key technology that provides direct insight into cell metabolism, cell dynamics and protein activity. However, determining the lifetimes of different fluorescent proteins requires the detection of a relatively large number of photons, hence slowing down total acquisition times. Moreover, there are many cases, for example in studies of cell collectives, where wide-field imaging is desired. We report scan-less wide-field FLIM based on a 0.5 Megapixel resolution, time-gated Single Photon Avalanche Diode (SPAD) camera, with acquisition rates up to 1 Hz. Fluorescence lifetime estimation is performed via a pre-trained artificial neural network with 1000-fold improvement in processing times compared to standard least squares fitting techniques. We utilised our system to image HT1080 -human fibrosarcoma cell line as well as Convallaria. The results show promise for real-time FLIM and a viable route towards multi-megapixel fluorescence lifetime images, with a proof-of-principle mosaic image shown with 3.6 megapixels.

show abstract

CMOS sensors for fluorescence lifetime imaging

Cited by 5 publications

References 85 publications

Fluorescence lifetime imaging with a megapixel SPAD camera and neural network lifetime estimation

Fluorescence lifetime imaging with a megapixel SPAD camera and neural network lifetime estimation

Auto-Phase-Locked Time-Resolved Luminescence Detection: Principles, Applications, and Prospects

Wide-field Fluorescence Lifetime Imaging Microscopy with a High-Speed Mega-pixel SPAD Camera

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