Graphene displays properties that make it appealing for neuroregenerative medicine, yet its interaction with peripheral neurons has been scarcely investigated. Here, we culture on graphene two established models for peripheral neurons: PC12 cells and DRG primary neurons. We perform a nano-resolved analysis of polymeric coatings on graphene and combine optical microscopy and viability assays to assess the material cytocompatibility and influence on differentiation. We find that differentiated PC12 cells display a remarkably increased neurite length on graphene (up to 27%) with respect to controls. Notably, DRG primary neurons survive both on bare and coated graphene. They present dense axonal networks on coated graphene, while they form cell islets characterized by dense axonal bundles on uncoated graphene. These findings indicate that graphene holds potential for nerve tissue regeneration and might pave the road to novel concepts of active nerve conduits.

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Peripheral Neuron Survival and Outgrowth on Graphene

The pinned photodiode is the primary photodetector structure used in most CCD and CMOS image sensors. This paper reviews the development, physics, and technology of the pinned photodiode.

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A Review of the Pinned Photodiode for CCD and CMOS Image Sensors

This paper investigates terahertz detectors fabricated in a low-cost 130 nm silicon CMOS technology. We show that the detectors consisting of a nMOS field effect transistor as rectifying element and an integrated bow-tie coupling antenna achieve a record responsivity above 5 kV/W and a noise equivalent power below 10 pW/Hz(0.5) in the important atmospheric window around 300 GHz and at room temperature. We demonstrate furthermore that the same detectors are efficient for imaging in a very wide frequency range from ~0.27 THz up to 1.05 THz. These results pave the way towards high sensitivity focal plane arrays in silicon for terahertz imaging.

Broadband terahertz imaging with highly sensitive silicon CMOS detectors

Single-photon avalanche diode (SPAD) arrays are solid-state detectors that offer imaging capabilities at the level of individual photons, with unparalleled photon counting and time-resolved performance. This fascinating technology has progressed at a very fast pace in the past 15 years, since its inception in standard CMOS technology in 2003. A host of architectures have been investigated, ranging from simpler implementations, based solely on off-chip data processing, to progressively "smarter" sensors including on-chip, or even pixel level, time-stamping and processing capabilities. As the technology has matured, a range of biophotonics applications have been explored, including (endoscopic) FLIM, (multibeam multiphoton) FLIM-FRET, SPIM-FCS, super-resolution microscopy, time-resolved Raman spectroscopy, NIROT and PET. We will review some representative sensors and their corresponding applications, including the most relevant challenges faced by chip designers and end-users. Finally, we will provide an outlook on the future of this fascinating technology.

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Single-photon avalanche diode imagers in biophotonics: review and outlook

We introduce a 512 × 424 time-of-flight (TOF) depth image sensor designed in a TSMC 0.13 μm LP 1P5M CMOS process, suitable for use in Microsoft Kinect for XBOX ONE. The 10 μm × 10 μm pixel incorporates a TOF detector that operates using the quantum efficiency modulation (QEM) technique at high modulation frequencies of up to 130 MHz, achieves a modulation contrast of 67% at 50 MHz and a responsivity of 0.14 A/W at 860 nm. The TOF sensor includes a 2 GS/s 10 bit signal path, which is used for the high ADC bandwidth requirements of the system that requires many ADC conversions per frame. The chip also comprises a clock generation circuit featuring a programmable phase and frequency clock generator with 312.5-ps phase step resolution derived from a 1.6 GHz oscillator. An integrated shutter engine and a programmable digital micro-sequencer allows an extremely flexible multi-gain/multi-shutter and multi-frequency/multi-phase operation. All chip data is transferred using two 4-lane MIPI D-PHY interfaces with a total of 8 Gb/s input/output bandwidth. The reported experimental results demonstrate a wide depth range of operation (0.8–4.2 m), small accuracy error ( $ 1%), very low depth uncertainty ( $ 0.5% of actual distance), and very high dynamic range ( $>$ 64 dB).

A 0.13 μm CMOS System-on-Chip for a 512 × 424 Time-of-Flight Image Sensor With Multi-Frequency Photo-Demodulation up to 130 MHz and 2 GS/s ADC

An 8 × 16 pixel array based on CMOS small-area silicon photomultipliers (mini-SiPMs) detectors for PET applications is reported. Each pixel is 570 × 610 μm2 in size and contains four digital mini-SiPMs, for a total of 720 SPADs, resulting in a full chip fill-factor of 35.7%. For each gamma detection, the pixel provides the total detected energy and a timestamp, obtained through two 7-b counters and two 12-b 64-ps TDCs. An adder tree overlaid on top of the pixel array sums the sensor total counts at up to 100 Msamples/s, which are then used for detecting the asynchronous gamma events on-chip, while also being output in real-time. Characterization of gamma detection performance with an 3 × 3 × 5 mm3 LYSO scintillator at 20°C is reported, showing a 511-keV gamma energy resolution of 10.9% and a coincidence timing resolution of 399 ps.

A Fully Digital 8 $\,\times\,$ 16 SiPM Array for PET Applications With Per-Pixel TDCs and Real-Time Energy Output

This paper describes a 64 $\times $ 64-pixel 3-D imager based on single-photon avalanche diodes (SPADs) for long-range applications, such as spacecraft navigation and landing. Each 60- $\mu \text{m}$ pixel includes eight SPADs combined as a digital silicon photomultiplier, a triggering logic for photons temporal correlation, a 250-ps 16-b time-to-digital converter, and an intensity counter, with an overall 26.5% fill factor. The sensor provides time-of-flight and intensity information even with a background intensity up to 100 MPhotons/s/pixel. The sensor can work in imaging (short range, 3-D image) and altimeter (long range, single point) modes, achieving up to 300-m and 6-km maximum distance with <0.2-m and <0.5-m precision, respectively, consuming less than 100 mW.

A 64 $\times$ 64-Pixels Digital Silicon Photomultiplier Direct TOF Sensor With 100-MPhotons/s/pixel Background Rejection and Imaging/Altimeter Mode With 0.14% Precision Up To 6 km for Spacecraft Navigation and Landing

A single-photon, time-gated, $160 \times 120 $ pixel imager is presented for its application in fluorescence lifetime imaging microscopy. Exploiting single-photon avalanche diodes and an extremely compact pixel circuitry—only seven MOSFETs and one MOSCAP—the imager is capable of gathering information about photon position, number, and time distribution, enabling cost-effective devices for scientific imaging applications. This is achieved thanks to the photon counting and time-gating capabilities implemented in the analog domain, which in turn enable a $15\;{\upmu}{\text{m}}$ pixel with a 21% fill-factor. A reconfigurable column circuitry supports both the analog conventional readout and a self-referenced analog-to-digital conversion, able to cancel out the pixel-to-pixel nonuniformities, and speeding up the framerate to 486 fps. The imager, featuring also a delay locked loop to stabilize the internal waveform generation for reliable timing performance, has been implemented in a standard high-voltage $0.35\;{\upmu}{\text{m}}$ CMOS technology. Measurements in a fluorescent lifetime setup have been performed, comparing the results with single-point acquisitions made with commercial time-correlated equipment.

A $160 \times 120$ Pixel Analog-Counting Single-Photon Imager With Time-Gating and Self-Referenced Column-Parallel A/D Conversion for Fluorescence Lifetime Imaging

This paper presents the design and characterization of a lock-in pixel array based on a buried channel photo-detector aimed at time-of-flight range imaging. The proposed photo-demodulator has been integrated in a 10-μm pixel pitch with a fill factor of 24%, and is capable of a maximum demodulation frequency of 50 MHz with a contrast of 29.5%. The sensor has been fabricated in a 0.18-μm CMOS imaging technology and assembled in a range camera system setup. The system provides a stream of three-dimensional images at 5-20 fps on a 3-6 m range, with a linearity error lower than 0.7% and a repeatability of 5-16 cm, while the best achievable precision is 2.7 cm at a 50-MHz modulation frequency.

A Range Image Sensor Based on 10- $\mu{\hbox {m}}$ Lock-In Pixels in 0.18- $\mu$ m CMOS Imaging Technology

THz Detectors 1 Quantum Well Photodetectors Fabrizio Castellano. 1.1 Fundamentals of photoconductors and photodiodes. 1.2 Semiconductor quantum wells. 1.3 Intersubband transitions. 1.4 Transport in multi-quantum-well systems. 1.5 Quantum well detectors. 1.6 Quantum dot detectors. 2 Bolometric Detectors Francois Simoens. 2.1 Bolometric detection. 2.2 Cooled THz bolometers. 2.3 Uncooled THz bolometers. 2.4 Conclusions. 2.5 Acknowledgements. 3 Terahertz Plasma Field-Effect Transistors Wojciech Knap, Dominique Coquillat, Nina Dyakonova, Dmitry But, Taiichi Otsuji and Frederic Teppe. 3.1 Introduction. 3.2 Experiments on THz Emission from Field Effect Transistors. 3.3 Experiments on THz Detection by Field Effect Transistors. 3.4 Detection by double grating gate FETs. 3.5 Summary. THz Sources. 4 Quantum Cascade Lasers Douglas Paul. 4.1 Background. 4.2 Quantum wells and quantum mechanical tunneling. 4.3 QCL lasing requirements. 4.4 Gain in quantum cascade lasers. 4.5 Active region designs. 4.6 Waveguide designs and losses. 4.7 Exemplar experimental laser results. 4.8 Future requirements from THz quantum cascade lasers. 4.9 Summary. 5 Relativistic Electrons Based Sources Andrea Doria. 5.1 The Electron Photon Interaction. 5.2 The Free Electron Laser (FEL) Mechanism. 5.3 Compact FELs. 5.4 The Frascati FEL Facility. 5.5 The Compact Advanced THz Source (CATS). 6 Non-linear Optical Generation Graeme Malcolm, David A. Walsh, Marc Chateauneuf. 6.1 Intracavity THz generation in OPOs. 6.2 Application of Intracavity THz OPO in stand-off spectroscopy. Systems and Applications. 7 THz Control with Metamaterials David R. S. Cumming, Timothy D. Drysdale, James P. Grant. 7.1 Diffractive optics. 7.2 Polarisation control. 7.3 Terahertz filters. 7.4 Metamaterials and surface plasmon resonance. 7.5 Summary. 8 Time Domain Spectroscopy Jean-Francois Roux, Frederic Garet, Jean-Louis Coutaz. 8.1 Introduction. 8.2 Principles of THz-TDS. 8.3 Generation and detection of short electromagnetic pulses. 8.4 Characteristics of a TDS setup. 8.5 Principles for extraction of optical parameters from THz-TDS measurements. 8.6 Examples of applications of THz-TDS. 8.7 Uncertainties and precision of THz-TDS. 8.8 Comparison with FTIR measurements. 8.9 Conclusions. 9 Security and Safety Roger Appleby, Martyn Chamberlain. 9.1 Overview. 9.2 Nature of security threats, ethical considerations. 9.3 Physical principles. 9.4 Review of previous topical reviews (2006-2010). 9.5 Review of available commercial and near-to-market systems. 9.6 New developments. 9.7 Terahertz safety. 9.8 Overall conclusions.

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Matteo Perenzoni

Papers

A Fully Digital 8 $\,\times\,$ 16 SiPM Array for PET Applications With Per-Pixel TDCs and Real-Time Energy Output

A 64 $\times$ 64-Pixels Digital Silicon Photomultiplier Direct TOF Sensor With 100-MPhotons/s/pixel Background Rejection and Imaging/Altimeter Mode With 0.14% Precision Up To 6 km for Spacecraft Navigation and Landing

A $160 \times 120$ Pixel Analog-Counting Single-Photon Imager With Time-Gating and Self-Referenced Column-Parallel A/D Conversion for Fluorescence Lifetime Imaging

A Range Image Sensor Based on 10- $\mu{\hbox {m}}$ Lock-In Pixels in 0.18- $\mu$ m CMOS Imaging Technology

Physics and applications of terahertz radiation