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Fluorescence correlation spectroscopy (FCS) is a well-established technique to study binding interactions or the diffusion of fluorescently labeled biomolecules in vitro and in vivo. Fast FCS experiments require parallel data acquisition and analysis which can be achieved by exploiting a multi-channel Single Photon Avalanche Diode (SPAD) array and a corresponding multi-input correlator. This paper reports a 32-channel FPGA based correlator able to perform 32 auto/cross-correlations simultaneously over a lag-time ranging from 10 ns up to 150 ms. The correlator is included in a 32 x 1S P A D array module, providing a compact and flexible instrument for high throughput FCS experiments. However, some inherent features of SPAD arrays, namely afterpulsing and optical crosstalk effects, may introduce distortions in the measurement of auto- and cross-correlation functions. We investigated these limitations to assess their impact on the module and evaluate possible workarounds. [ABSTRACT FROM AUTHOR]

Single photon avalanche diodes (SPADs) have been subject to a fast improvement in recent years. In particular, custom technologies specifically developed to fabricate SPAD devices give the designer the freedom to pursue the best detector performance required by applications. A significant breakthrough in this field is represented by the recent introduction of a red enhanced SPAD (RE-SPAD) technology, capable of attaining a good photon detection efficiency in the near infrared range (e.g. 40% at a wavelength of 800 nm) while maintaining a remarkable timing resolution of about 100ps full width at half maximum. Being planar, the RE-SPAD custom technology opened the way to the development of SPAD arrays particularly suited for demanding applications in the field of life sciences. However, to achieve such excellent performance custom SPAD detectors must be operated with an external active quenching circuit (AQC) designed on purpose. Next steps toward the development of compact and practical multichannel systems will require a new generation of monolithically integrated AQC arrays. In this paper we present a new, fully integrated AQC fabricated in a high-voltage 0.18 µm CMOS technology able to provide quenching pulses up to 50 Volts with fast leading and trailing edges. Although specifically designed for optimal operation of RE-SPAD devices, the new AQC is quite versatile: it can be used with any SPAD detector, regardless its fabrication technology, reaching remarkable count rates up to 80 Mcounts/s and generating a photon detection pulse with a timing jitter as low as 119 ps full width at half maximum. The compact design of our circuit has been specifically laid out to make this IC a suitable building block for monolithically integrated AQC arrays.

In this letter we present a compact photon detection module, based on an 8×8 array of single-photon avalanche diodes (SPADs). The use of a dedicated silicon technology for the fabrication of the sensors allows us to combine large active areas (50-μm diameter), high photon detection efficiency (49% at 550-nm wavelength) and low dark count rate. Thanks to a fully parallel architecture, the module provides voltage pulses synchronous to each photon detection for a maximum global count rate exceeding 1 Gcps. These properties makes the system suitable for operation in two different free-running modes. The first, suitable to acquire faint signals, allows multi-spot acquisitions and can be used to considerably reduce the measurement time in applications like single-molecule analysis. With the second it is possible to use all the pixels in a combined mode, to extend and move the dynamic range of the module to very high count rates and to attain number resolving capabilities.

In order to fulfill the requirements of many applications, we recently developed a new technology aimed at combining the advantages of traditional thin and thick silicon Single Photon Avalanche Diodes (SPAD). In particular we demonstrated single-pixel detectors with a remarkable improvement in the Photon Detection Efficiency in the red/near-infrared spectrum (e.g. 40% at 800nm) while maintaining a timing jitter better than 100ps. In this paper we discuss the limitations of such Red-Enhanced (RE) technology from the point of view of the fabrication of small arrays of SPAD and we propose modifications to the structure aimed at overcoming these issues. We also report the first preliminary experimental results attained on devices fabricated adopting the improved structure., Competing Interests: M. Ghioni discloses equity in Micro Photon Devices S.r.l. (MPD).

Silicon single-photon avalanche diodes (SPADs) are nowadays a solid-state alternative to photomultiplier tubes (PMTs) in single-photon counting (SPC) and time-correlated single-photon counting (TCSPC) over the visible spectral range up to 1-mum wavelength. SPADs implemented in planar technology compatible with CMOS circuits offer typical advantages of microelectronic devices (small size, ruggedness, low voltage, low power, etc.). Furthermore, they have inherently higher photon detection efficiency, since they do not rely on electron emission in vacuum from a photocathode as do PMTs, but instead on the internal photoelectric effect. However, PMTs offer much wider sensitive area, which greatly simplifies the design of optical systems; they also attain remarkable performance at high counting rate, and offer picosecond timing resolution with microchannel plate models. In order to make SPAD detectors more competitive in a broader range of SPC and TCSPC applications, it is necessary to face several issues in the semiconductor device design and technology. Such issues will be discussed in the context of the two possible approaches to such a challenge: employing a standard industrial high-voltage CMOS technology or developing a dedicated CMOS-compatible technology. Advances recently attained in the development of SPAD detectors will be outlined and discussed with reference to both single-element detectors and integrated detector arrays. [ABSTRACT FROM PUBLISHER]

This paper presents a novel, compact, and energy-efficient hysteretic boost converter that employs an anti-phase AC-coupling emulate current control. The proposed scheme utilizes a two-transistor current emulator and a comparator, which allow for fast transient responses and tight closed-loop regulations. This converter was fabricated using a 180 nm CMOS process and was capable of regulating a 5 V output with a 400 mA load capacity from an input voltage range of 2.7 V to 4.5 V. The experimental results demonstrate that the proposed anti-phase AC-coupling emulate current controlling and single hysteretic comparator controlling scheme show lower power/circuit complexity and better static and transient performance. Specifically, under load transitions ranging from 0 mA to 300 mA, the converter exhibits over/undershoot voltages of 38 mV and −42 mV, respectively. Furthermore, the measured load and line regulation performances are 5 mV/A and 2.3 mV/V, respectively. Overall, this study offers a practical and efficient solution for boosting voltage levels while maintaining stable and precise regulation. [ABSTRACT FROM AUTHOR]

It is shown that the integration of a single-photon avalanche diode (SPAD) together with a BiCMOS gating circuit on one chip reduces the parasitic capacitance a lot and therefore reduces the avalanche build-up time. The capacitance of two bondpads, which are necessary for the connection of an SPAD chip and a gating chip, are eliminated by the integration. The gating voltage transients of the SPAD are measured using an integrated mini-pad and a picoprobe. Furthermore, the gating voltage transients of a CMOS gating circuit and of the BiCMOS gating circuit are compared for the same integrated SPAD. The extension of the 0.35 μ m CMOS process by an NPN transistor process module enabled the BiCMOS gating circuit. The avalanche build-up time of the SPAD is reduced to 1.6 ns due to the integration compared to about 3 ns for a wire-bonded off-chip SPAD using the same n + and p-well as well as the same 0.35 μ m technology. [ABSTRACT FROM AUTHOR]

Introduction: Endometriosis is considered as a precancerous lesion for OCCC; however its prognostic significance remains controversial. This study aims to evaluate the prognostic significance of endometriosis in patients with ovarian clear cell carcinoma (OCCC) and analyze the impact of other clinical pathological features on prognosis. Additionally, we also assess the role of laparoscopic surgery and chemotherapy in OCCC, hoping to provide evidence for improving the clinical diagnosis and treatment of OCCC. Methods: A retrospective analysis was conducted on medical records of 105 OCCC patients diagnosed and treated at the Gynecologic Cancer Center of Hubei Cancer Hospital in China from 2013 to 2022. Based on the presence or absence of endometriosis, OCCC patients were divided into two groups: a group with ovarian endometriosis consisting of 44 cases (41.9%) (EC-positive group) and a group without ovarian endometriosis consisting of 61 cases (58.1%)(EC-negative group). Clinical pathological characteristics, progression-free survival (PFS), and overall survival (OS) were compared between the two groups. Results: There were no statistically significant differences between the two groups in terms of age, CA125, tumor size, FIGO stage, adjuvant chemotherapy regimen, or chemotherapy efficacy (P>0.05). Residual tumor after surgery, staging, site invasion involvement, presence of ascites, positive cytology in ascitic fluid, lymph node metastasis, and chemotherapy efficacy were predictive factors for recurrence among patients with statistical significance (P<0.10); chemotherapy efficacy remained as independent predictors for recurrence (P<0.05); staging and chemotherapy efficacy remained as independent predictors for survival (P<0.05). There was no statistically significant difference observed between both groups regarding OS or PFS. Conclusion: In this study, co-existing endometriosis was not a prognostic factor for survival in patients with OCCC. The most important predictors of OS and PFS were FIGO stage and chemotherapy sensitivity. The intrinsic link between endometriosis and OCCC requires larger, better-designed prospective studies to draw more definitive conclusions. [ABSTRACT FROM AUTHOR]

Designing SPADs with high sensitivity in a wide wavelength range is crucial since the applications utilizing SPAD-based sensors target different parts of the spectrum. Here, we introduce a novel technique to achieve a wider sensitivity spectrum through the insertion of a second multiplication region into the depletion region. Thanks to the proposed method, at 5.5 V excess bias voltage, the fabricated devices achieved a PDP of 78% peak at 500 nm and 25.5% at 850 nm wavelength. At the same excess bias, we measured a normalized noise of 3.7 cps/μm2 and a jitter of 165 ps at 517 nm FWHM. [ABSTRACT FROM AUTHOR]

Introduction: In order to comprehensive understanding of the characteristics of high-risk HPV-negative cervical cancer and aiming to provide certain evidence in the diagnosis and treatment of this kind of disease, the clinical and pathological characteristics of high-risk HPV-negative (hr-HPV-negative) cervical cancer was evaluated through systematic review and meta-analysis. Methods: We employed a systematic search strategy incorporating both MeSH terms and free words across multiple databases including PubMed, Embase, Cochrane Library, Web of Science, CNKI and Wanfang. The strategy was specifically designed to identify articles investigating risk factors or clinical characteristics of hr-HPV-negative cervical cancer. Our database search spanned from their inception until October 2023. The literature selection and data collection processes were guided by predetermined inclusion and exclusion criteria. Each included research was independently evaluated by two reviewers using the Newcastle-Ottawa Scale (NOS) and a meta-analysis was conducted utilizing RevMan5.4. Results: In total, nine studies published between 2013 and 2020 were included. The risk of lymph node metastasis was notably higher in hr-HPV-negative cervical cancer patients compared to hr-HPV-positive counterparts [RR=1.99, 95%CI (1.46-2.72), P<0.0001]. It was found that clinical staging of Ib2 or higher grade was significantly increased in hr-HPV-negative cervical cancer patients, as reported by seven studies [RR=1.42, 95%CI (1.15-1.77), P=0.0001]. Nonsquamous carcinoma incidence, reported in seven studies, was significantly higher in hr-HPV-negative patients [RR=2.56, 95%CI (1.63-4.01), P=0.001]. Adenocarcinoma incidence was also significantly higher in hr-HPV-negative cervical cancer patients [RR=2.36, 95%CI (1.44-3.89), P=0.005]. Conclusions: Cervical cancer patients not infected by hr-HPV exhibited increased rates of lymph node metastasis, adenocarcinoma, and nonsquamous carcinoma. And they were often diagnosed at more advanced stages. These variables suggest that hr-HPV-negative cervical cancer patients presented with a more severe health status at the time of their initial cancer diagnosis. [ABSTRACT FROM AUTHOR]

Photodetectors play a critical role in space lidars designed for scientific investigations from orbit around planetary bodies. The detectors must be highly sensitive due to the long range of measurements and tight constraints on the size, weight, and power of the instrument. The detectors must also be space radiation tolerant over multi-year mission lifetimes with no significant performance degradation. Early space lidars used diode-pumped Nd:YAG lasers with a single beam for range and atmospheric backscattering measurements at 1064 nm or its frequency harmonics. The photodetectors used were single-element photomultiplier tubes and infrared performance-enhanced silicon avalanche photodiodes. Space lidars have advanced to multiple beams for surface topographic mapping and active infrared spectroscopic measurements of atmospheric species and surface composition, which demand increased performance and new capabilities for lidar detectors. Higher sensitivity detectors are required so that multi-beam and multi-wavelength measurements can be performed without increasing the laser and instrument power. Pixelated photodetectors are needed so that a single detector assembly can be used for simultaneous multi-channel measurements. Photon-counting photodetectors are needed for active spectroscopy measurements from short-wave infrared to mid-wave infrared. HgCdTe avalanche photodiode arrays have emerged recently as a promising technology to fill these needs. This paper gives a review of the photodetectors used in past and present lidars and the development and outlook of HgCdTe APD arrays for future space lidars. [ABSTRACT FROM AUTHOR]

Solution-based single-molecule fluorescence spectroscopy is a powerful experimental tool with applications in cell biology, biochemistry and biophysics. The basic feature of this technique is to excite and collect light from a very small volume and work in a low concentration regime resulting in rare burst-like events corresponding to the transit of a single molecule. Detecting photon bursts is a challenging task: the small number of emitted photons in each burst calls for high detector sensitivity. Bursts are very brief, requiring detectors with fast response time and capable of sustaining high count rates. Finally, many bursts need to be accumulated to achieve proper statistical accuracy, resulting in long measurement time unless parallelization strategies are implemented to speed up data acquisition. In this paper we will show that silicon single-photon avalanche diodes (SPADs) best meet the needs of single-molecule detection. We will review the key SPAD parameters and highlight the issues to be addressed in their design, fabrication and operation. After surveying the state-of-the-art SPAD technologies, we will describe our recent progress towards increasing the throughput of single-molecule fluorescence spectroscopy in solution using parallel arrays of SPADs. The potential of this approach is illustrated with single-molecule Förster resonance energy transfer measurements.

Single photon avalanche diodes (SPADs) are avalanche photodiodes specifically designed for reverse bias operation above the breakdown voltage and used for detecting single optical photons. A new silicon epitaxial device structure was designed to give improved timing performance with respect to previous SPADs. Extensive tests were carried out in order to establish the timing resolution of the device in time correlated photon counting (TCPC). The timing resolution of the SPAD in terms of its full-width at half-maximum (FWHM) contribution to the overall instrumental response width is 20 ps with the detector cooled to -65 °C, and 28 ps at room temperature. This is the highest resolution so far reported for solid-state single-photon detectors. In vacuum tubes, comparable results are obtained only with special microchannel-plate photomultipliers (MCP-PMT). Results from time-resolved photoluminescence measurements in GaAs demonstrate the power of the TCPC technique when used with the new SPAD detector. With the excellent timing resolution of the SPAD and the well-known advantages of TCPC systems (high sensitivity, linearity, etc.), various applications are foreseen in areas so far dominated by streak cameras. [ABSTRACT FROM AUTHOR]