A High-Throughput Time-Resolved Mini-Silicon Photomultiplier With Embedded Fluorescence Lifetime Estimation in 0.13 μm CMOS

被引:75
|
作者
Tyndall, David [1 ,2 ,3 ]
Rae, Bruce R. [4 ]
Li, David Day-Uei [5 ]
Arlt, Jochen [6 ]
Johnston, Abigail [6 ]
Richardson, Justin A. [3 ]
Henderson, Robert K. [1 ,2 ]
机构
[1] Univ Edinburgh, Sch Engn, CMOS Sensors & Syst Grp, Edinburgh EH9 3JL, Midlothian, Scotland
[2] Univ Edinburgh, Sch Engn, Inst Integrated Micro & Nano Syst, Edinburgh EH9 3JL, Midlothian, Scotland
[3] Dialog Semicond, Edinburgh EH1 3DQ, Midlothian, Scotland
[4] STMicroelectronics, Edinburgh EH12 7BF, Midlothian, Scotland
[5] Univ Sussex, Sch Engn & Informat, Dept Engn & Design, Brighton BN1 9QT, E Sussex, England
[6] Univ Edinburgh, Sch Phys & Astron, COSMIC, Edinburgh EH9 3JZ, Midlothian, Scotland
基金
英国工程与自然科学研究理事会;
关键词
Biosensors; silicon photomultipliers (SiPMs); single photon avalanche diodes (SPADs); time-correlated single photon counting (TCSPC); time domain fluorescence lifetime; DOMAIN; ARRAY;
D O I
10.1109/TBCAS.2012.2222639
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
We describe a miniaturized, high-throughput, time-resolved fluorescence lifetime sensor implemented in a 0.13 mu m CMOS process, combining single photon detection, multiple channel timing and embedded pre-processing of fluorescence lifetime estimations on a single device. Detection is achieved using an array of single photon avalanche diodes (SPADs) arranged in a digital silicon photomultiplier (SiPM) architecture with 400 ps output pulses and a 10% fill-factor. An array of time-to-digital converters (TDCs) with approximate to 50 ps resolution records up to 8 photon events during each excitation period. Data from the TDC array is then processed using a centre-of-mass method (CMM) pre-calculation to produce fluorescence lifetime estimations in real-time. The sensor is believed to be the first reported implementation of embedded fluorescence lifetime estimation. The system is demonstrated in a practical laboratory environment with measurements of a variety of fluorescent dyes with different single exponential lifetimes, successfully showing the sensor's ability to overcome the classic pile-up limitation of time-correlated single photon counting (TCSPC) by over an order of magnitude.
引用
收藏
页码:562 / 570
页数:9
相关论文
共 50 条
  • [31] Discovery of Enzyme Modulators via High-Throughput Time-Resolved FRET in Living Cells
    Gruber, Simon J.
    Cornea, Razvan L.
    Li, Ji
    Peterson, Kurt C.
    Schaaf, Tory M.
    Gillispie, Gregory D.
    Dahl, Russell
    Zsebo, Krisztina M.
    Robia, Seth L.
    Thomas, David D.
    JOURNAL OF BIOMOLECULAR SCREENING, 2014, 19 (02) : 215 - 222
  • [32] Time-Resolved Luminescent High-Throughput Screening Platform for Lysosomotropic Compounds in Living Cells
    Wu, Ke-Jia
    Wu, Chun
    Chen, Feng
    Cheng, Sha-Sha
    Ma, Dik-Lung
    Leung, Chung-Hang
    ACS SENSORS, 2021, 6 (01): : 166 - 174
  • [33] High-throughput time-resolved morphology screening in bacteria reveals phenotypic responses to antibiotics
    Zahir, Taiyeb
    Camacho, Rafael
    Vitale, Raffaele
    Ruckebusch, Cyril
    Hofkens, Johan
    Fauyart, Maarten
    Michiels, Jan
    COMMUNICATIONS BIOLOGY, 2019, 2
  • [34] Discovery of Enzyme Modulators via High-Throughput Time-Resolved FRET in Living Cells
    Gruber, Simon J.
    Cornea, Razvan L.
    Peterson, Kurt C.
    Gillispie, Gregory D.
    Robia, Seth L.
    Thomas, David D.
    BIOPHYSICAL JOURNAL, 2014, 106 (02) : 427A - 428A
  • [35] Time-resolved fluorescence energy transfer DNA helicase assays for high throughput screening
    Earnshaw, DL
    Moore, KJ
    Greenwood, CJ
    Djaballah, H
    Jurewicz, AJ
    Murray, KJ
    Pope, AJ
    JOURNAL OF BIOMOLECULAR SCREENING, 1999, 4 (05) : 239 - 248
  • [36] High throughput screening of β-amyloid secretion inhibitors using homogenous time-resolved fluorescence
    Imbimbo, BP
    Albrecht, H
    Zbinden, P
    Rizzi, A
    Villetti, G
    Riccardi, B
    Puccini, P
    Catinella, S
    NEUROBIOLOGY OF AGING, 2004, 25 : S572 - S572
  • [37] High throughput screening of β-amyloid secretion inhibitors using homogenous time-resolved fluorescence
    Albrecht, H
    Zbinden, P
    Rizzi, A
    Villetti, G
    Riccardi, B
    Puccini, P
    Catinella, S
    Imbimbo, BP
    COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING, 2004, 7 (08) : 745 - 756
  • [38] High-Throughput 0.13-μm CMOS Lattice Reduction Core Supporting 880 Mb/s Detection
    Shabany, Mahdi
    Youssef, Ameer
    Gulak, Glenn
    IEEE TRANSACTIONS ON VERY LARGE SCALE INTEGRATION (VLSI) SYSTEMS, 2013, 21 (05) : 848 - 861
  • [39] Identification of Pregnane X Receptor Ligands Using Time-Resolved Fluorescence Resonance Energy Transfer and Quantitative High-Throughput Screening
    Shukla, Sunita J.
    Nguyen, Dac-Trung
    MacArthur, Ryan
    Simeonov, Anton
    Frazee, William J.
    Hallis, Tina M.
    Marks, Bryan D.
    Singh, Upinder
    Eliason, Hildegard C.
    Printen, John
    Austin, Christopher P.
    Inglese, James
    Auld, Douglas S.
    ASSAY AND DRUG DEVELOPMENT TECHNOLOGIES, 2009, 7 (02) : 143 - 169
  • [40] High-throughput screening - Evolution of Homogeneous Time Resolved Fluorescence (HTRF) technology for HTS
    Grepin, C
    Pernelle, C
    DRUG DISCOVERY TODAY, 2000, 5 (05) : 212 - 214