Room temperature, broadly tunable, electrically pumped semiconductor sources in the terahertz spectral range, similar in operation simplicity to diode lasers, are highly desired for applications. An emerging technology in this area are sources based on intracavity difference-frequency generation in dual-wavelength mid-infrared quantum cascade lasers. Here we report terahertz quantum cascade laser sources based on an optimized non-collinear Cherenkov difference-frequency generation scheme that demonstrates dramatic improvements in performance. Devices emitting at 4 THz display a mid-infrared-to-terahertz conversion efficiency in excess of 0.6 mW W À 2 and provide nearly 0.12 mW of peak power output. Devices emitting at 2 and 3 THz fabricated on the same chip display 0.09 and 0.4 mW W À 2 conversion efficiencies at room temperature, respectively. High terahertzgeneration efficiency and relaxed phase-matching conditions offered by the Cherenkov scheme allowed us to demonstrate, for the first time, an external-cavity terahertz quantum cascade laser source tunable between 1.70 and 5.25 THz.

We discuss the design and operation of widely-tunable terahertz sources based on Cherenkov intra-cavity difference-frequency generation in mid-infrared quantum cascade lasers. Laser chips are integrated into a Littrow-type external cavity system. Devices demonstrate continuous terahertz emission tuning at room temperature with a record tuning range from 1.2 THz to 5.9 THz and peak power output varying between 5 and 90 μW, depending on the operating frequency. Beam steering of terahertz Cherenkov emission with frequency is suppressed and mid-infrared-to-terahertz conversion efficiency is improved by bonding devices onto highresistivity silicon substrates that have virtually no refractive index dispersion and vanishinglysmall optical loss in 1-6 THz range.

Background There is currently no research on the diagnostic value of metagenomic next-generation sequencing (mNGS) for a single pathogens in CSF. The aim of this study was to analyse the value of mNGS for identifying Streptococcus pneumoniae ( S. pneumoniae ) in paediatric bacterial meningitis. Methods Bacterial meningitis (BM) cases from October 23, 2014, to December 31, 2016, and December 1, 2017, to July 31, 2018 at Beijing Children’s Hospital were reviewed. Clinical features and pathogens were analysed. Results We diagnosed 135 patients with BM in this study. A total of 43 S. pneumoniae were identified by combination methods. 26/135 (19.3%) patients had positive results in S. pneumoniae by blood and/or cerebrospinal fluid (CSF) culture. Alere BinaxNow® Streptococcus pneumoniae Antigen test was positive in 35/135(25.9%) cases. 32/135 (23.7%) S. pneumoniae were identified by mNGS. Six CSF samples were identified as S. pneumoniae only by mNGS technology. Taking culture as the gold standard, the sensitivity and specificity of mNGS for diagnosing S. pneumoniae meningitis were 73.1 and 88.1%, respectively. The positive predictive value (PPV) and negative predictive value (NPV) of diagnosing S. pneumoniae meningitis by mNGS were 59.4 and 93.2%, respectively. When comparison between mNGS and combined tests (culture and Alere BinaxNow® Streptococcus pneumoniae Antigen test), the sensitivity and specificity of mNGS for S. pneumoniae identification were 70.3 and 93.9%, the PPV and NPV in the identification of S. pneumoniae by mNGS were 81.4 and 89.3%, respectively. The difference in number of unique reads of S. pneumoniae in from CSF sample (< 14 days onset) and CSF sample (> 14 days from onset) was statistically significant (170.5 VS. 13, P = 0.019). The difference in the collected time of CSF for culture and mNGS was statistically significant (4 days VS. 14 days, P < 0.001). Conclusions mNGS has high sensitivity and specificity for S. pneumoniae identification. The pathogen load (number of unique reads) of S. pneumonia is related to the CSF collection time. mNGS was less affected than culture by the use of antibiotics before CSF collection.

Terahertz quantum cascade laser (QCL) sources based on intra-cavity difference frequency generation are currently the only electrically pumped monolithic semiconductor light sources operating at room temperature in the 1–6-THz spectral range. Relying on the active regions with the giant second-order nonlinear susceptibility and the Cherenkov phase-matching scheme, these devices demonstrated drastic improvements in performance in the past several years and can now produce narrow-linewidth single-mode terahertz emission that is tunable from 1 to 6 THz with power output sufficient for imaging and spectroscopic applications. This paper reviews the progress of this technology. Recent efforts in wave function engineering using a new active region design based on a dual-upper-state concept led to a significant enhancement of the optical nonlinearity of the active region for efficient terahertz generation. The transfer of Cherenkov devices from their native semi-insulating InP substrates to high-resistivity silicon substrates resulted in a dramatic improvement in the outcoupling efficiency of terahertz radiation. Cherenkov terahertz QCL sources based on the dual-upper-state design have also been shown to exhibit ultra-broadband comb-like terahertz emission spectra with more than one octave of terahertz frequency span. The broadband terahertz QCL sources operating in continuous-wave mode produces the narrow inter-mode beat-note linewidth of 287 Hz, which indicates frequency comb operation of mid-infrared pumps and thus supports potential terahertz comb operation. Finally, we report the high-quality terahertz imaging obtained by a THz imaging system using terahertz QCL sources based on intra-cavity difference frequency generation.