title: High performance single photon avalanche diode using unmodified CMOS for sensing and imaging
Creators: name: Accarino, Claudio
Publisher: name: University of Glasgow
Year: 2019
Subjects: subject: Single photon avalanche diode (SPAD), CMOS, photo detector, image sensor, fluorescence, colorimetric assays, x-rays, electric fields, junctions, sensor arrays, photonics, electronics.

description: The measurement of weak optical signals is an important aspect in many science sectors including biology, chemistry, and nuclear physics. To this extent the collection of weak and fast decaying fluorescence signals, down to single photon level, currently relies on the use of bulky and expensive photomultiplier tube (PMT) detectors; charge-coupled devices (CCDs) and complementary metal-oxide semiconductor (CMOS) photodetectors have also been studied however they require extremely low noise circuitry and very long integration times. Single photon avalanche diodes (SPAD) offer the advantages of both low-cost CMOS technology and fast timing performance. A general problem is that relatively few technologies are available, and the major semiconductor companies are focusing on specialized technologies that are costly and not easily accessible, to make devices such as proximity sensors. Portable technologies for low-light applications in bio-related disciplines (i.e. fluorescence cancer detection) are still scarce. This work describes the research undertaken for the development of an integrated CMOS SPAD that was incorporated in a 64x64 array which formed the basis for a multiple sensing technology platform for fluorescence imaging and colorimetric assay. The strategy to develop this system, using a legacy 180 nm high voltage CMOS technology (using a process by AMS AG), implemented the following workflow: (1) Design a stand-alone SPAD with low dark count rate (DCR) and high photodetection probability (PDP) at blue-green wavelengths. (2) Full characterization of the stand-alone SPAD after design optimization. (3) Scaling of the sensor to an array of 64x64 SPADs with in-pixel readout electronics. (4) Develop protocols to interface the SPAD array with a laptop via a microcontroller for data readout. (5) Characterize and test the 64x64 SPAD array with fluorescent media. (6) Test the 64x64 SPAD array combined with a microfluidic network (designed and developed by Valerio F. Annese) as a colorimetric assay platform. (7) Test the 64x64 SPAD array for two additional applications, these being x-ray sensing (in collaboration with Prof Craig Buttar’s group at University of Glasgow) and color quality enhancement with flip-chip bonded plasmonic filters (developed by Dr Yash D. ii Shah in collaboration with Prof Gerrard Bullar at Heriot-Watt University, currently in progress and therefore discussed in future work). The full development of a stand-alone SPAD required the use of technology computer-aided design (TCAD) simulations, using Sentaurus TCAD by Synopsys, and two tapeout runs. The tapeout runs were submitted to AMS for fabrication. The first tapeout run contained 75 different test structures and the second run had 26 optimized structures derived from the first run. The final optimized stand-alone SPAD, based on a squared p+/shallow-n active junction with a shallow-p well into a deep p-well guard ring, has an active area of 134.56 µm2 , a breakdown voltage of 16.8 V, a DCR of 3.86 cps/µm2 with a PDP peak of 66% at 480 nm (blue) when operated at the maximum excess bias of 5 V. The DCR and PDP performance of the stand-alone SPAD compare favorably with those of other SPADs in the 180 nm technology node. An array of 64x64 pixels based on the stand-alone SPAD with the best performance was developed and manufactured during a third tapeout run. Based on the pixel pitch requirement for the two main applications, the designed array has a pixel pitch of 61.5 µm to ensure decent imaging resolution and to safely integrate a microfluidic network, without sacrificing any sensors (once the network is fully optimized). The 64x64 SPAD array, designed with an 8-bit in-pixel counter and a global shutter, showed an imaging resolution of 78.75 µm and a frame rate of 3 fps. Fluorescent imaging was successfully demonstrated by acquiring well contrasted images of fluorescein isothiocyanate (FITC) fluorophores, having similar fluorescence emission of human healthy cell, at different concentrations down to 900 pM with a signal to noise ratio (SNR) of 9.8 dB. Sarcosine assay in buffer solution was tested in the 64x64 SPAD array combined with a microfluidic network, resulting in a quantification limit (the minimum detectable concentration) of 3.1 µM. The 64x64 SPAD array successfully acquired x-ray images of a lead mask at different energies, demonstrating for the first-time x-ray imaging capability on CMOS SPADs without scintillation crystals. iii A mosaic plasmonic filter of randomly arranged blue, green and red covering the entire 64x64 pixels was designed and fabricated. Once flip-chip bonded onto the SPAD array it will provide a promising avenue to integration and miniaturization that would pave the way to multispectral imaging. Based on the demonstrated performance, the presented 64x64 SPAD array is an excellent candidate for the future development of portable, reliable and low-cost screening techniques for disease prevention and monitoring. The added value of multiple sensing allows the device to be implemented not only as mass screening technique but also as lab-on-a-chip for laboratory and point-of-care diagnostics (based on foundry availability).