自动量化的肿瘤-间质比预测胃癌新辅助化疗疗效

目的:探讨通过深度学习的方法来全自动定量评估术前活检标本的肿瘤-间质比(tumor-stroma ratio,TSR)是否可以预测胃癌患者新辅助化疗(neoadjuvant chemotherapy,NAC)疗效。方法:选取2013年3月至2020年3月在云南省肿瘤医院接受NAC治疗的胃癌患者的术前活检切片148张和手术切除切片43张。构建肿瘤区域分割模型和上皮-间质分割模型,使用手术切除切片训练和评估模型,在活检切片上预测,取二者预测结果的交集,根据TSR的定义得到TSR值。根据术后病理学肿瘤退缩分级(tumor regression grade,TRG)将所有患者分为反应良好者(TRG 0~1)和反应不良者(TRG 2~3)。采用单因素和多因素回归分析TSR与胃癌新辅助化疗疗效的相关性。结果:肿瘤组织分割模型的IOU(intersection over union)为0.94,上皮-间质分割模型的IOU为0.88。以44.93%和70.22%作为TSR的临界值,将患者分为低、中、高间质比组,三组之间反应良好者比例具有显著性差异(P<0.05)。多因素分析显示,TSR是治疗前对胃癌NAC反应的独立预测因子(OR=0.10,95%CI:0.03~0.32)。使用常规临床信息预测治疗响应的基础上,加入TSR三分类等级作为治疗响应的预测变量时,曲线下面积(area under curve,AUC)可从0.71提升至0.85。结论:该模型能够在病理切片上自动分割肿瘤区域、上皮区域和间质区域,并能够自动、准确的计算出TSR,同时发现基于此方法自动计算的TSR可以预测NAC疗效。

Sensitivity-enhanced surface plasmon resonance sensor utilizing a tungsten disulfide (WS_2) nanosheets overlayer

Tungsten disulfide(WS_2), as a representative layered transition metal dichalcogenide(TMDC) material, possesses important potential for applications in highly sensitive sensors. Here, a sensitivity-enhanced surface plasmon resonance(SPR) sensor with a metal film modified by an overlayer of WS_2 nanosheets is proposed and demonstrated. The SPR sensitivity is related to the thickness of the WS_2 overlayer, which can be tailored by coating a WS_2 ethanol suspension with different concentrations or by the number of times of repeated post-coating.Benefitting from its large surface area, high refractive index, and unique optoelectronic properties, the WS_2 nanosheet overlayer coated on the gold film significantly improves the sensing sensitivity. The highest sensitivity(up to 2459.3 nm∕RIU) in the experiment is achieved by coating the WS_2 suspension once. Compared to the case without a WS_2 overlayer, this result shows a sensitivity enhancement of 26.6%. The influence of the WS_2 nanosheet overlayer on the sensing performance improvement is analyzed and discussed. Moreover, the proposed WS_2 SPR sensor has a linear correlation coefficient of 99.76% in refractive index range of 1.333 to 1.360. Besides sensitivity enhancement, the WS_2 nanosheet overlayer is able to show additional advantages, such as protection of metal film from oxidation, tunability of the resonance wavelength region, biocompatibility, capability of vapor,and gas sensing.

Resonant enhancement of second harmonic generation in etchless thin film lithium niobate heteronanostructure

Lithium niobate has received interest in nonlinear frequency conversion due to its wide transparency window,from ultraviolet to mid-infrared spectral regions,and large second-order nonlinear susceptibility.However,its nanostructure is generally difficult to etch,resulting in low-Q resonance and lossy nanostructures for second harmonic generation.By applying the concept of bound states in the continuum,we performed theoretical and experimental investigations on high-Q resonant etchless thin-film lithium niobate with Si O_(2) nanostructures on top for highly efficient second harmonic generation.In the fabricated nanostructured devices,a resonance with a Q factor of 980 leads to the strong enhancement of second harmonic generation by over 1500 times compared with that in unpatterned lithium niobate thin film.Although the pump slightly deviates from central resonance,an absolute conversion efficiency of 6.87×10^(-7) can be achieved with the fundamental pump peak intensity of 44.65 MW/cm^(2),thus contributing to the normalized conversion efficiency of 1.54×10^(-5)cm^(2)/GW.Our work establishes an etchless lithium niobate device for various applications,such as integrated nonlinear nanophotonics,terahertz frequency generation,and quantum information processing.

Recent progress of second harmonic generation based on thin film lithium niobate [Invited]

Recently, nonlinear photonics has attracted considerable interest. Among the nonlinear effects, second harmonic generation(SHG) remains a hot research topic. The recent development of thin film lithium niobate(TFLN) technology has superior performances to the conventional counterparts. Herein, this review article reveals the recent progress of SHG based on TFLN and its integrated photonics. We mainly discuss and compare the different techniques of TFLN-based structures to boost the nonlinear performances assisted by localizing light in nanostructures and structured waveguides.Moreover, our conclusions and perspectives indicate that more efficient methods need to be further explored for higher SHG conversion efficiency on the TFLN platform.

Distance-controllable and direction-steerable opto-conveyor for targeting delivery

Opto-conveyors have attracted widespread interest in various fields because of their non-invasive and non-contact delivery of micro/nanoparticles.However,the flexible control of the delivery distance and the dynamic steering of the delivery direction,although very desirable in all-optical manipulation,have not yet been achieved by optoconveyors.Here,using a simple and cost-effective scheme of an elliptically focused laser beam obliquely irradiated on a substrate,a direction-steerable and distance-controllable opto-conveyor for the targeting delivery of microparticles is implemented.Theoretically,in the proposed scheme of the opto-conveyor,the transverse and longitudinal resultant forces of the optical gradient force and the optical scattering force result in the transverse confinement and the longitudinal transportation of microparticles,respectively.In this study,it is experimentally shown that the proposed opto-conveyor is capable of realizing the targeting delivery for microparticles.Additionally,the delivery distance of microparticles can be flexibly and precisely controlled by simply adjusting the irradiation time.By simply rotating the cylindrical lens,the proposed opto-conveyor is capable of steering the delivery direction flexibly within a large range of azimuthal angles,from-75°to 75°.This study also successfully demonstrated the real-time dynamic steering of the delivery direction from-45°to 45°with the dynamical rotation of the cylindrical lens.Owing to its simplicity,flexibility,and controllability,the proposed method is capable of creating new opportunities in bioassays as well as in drug delivery.

Ultra-compact on-chip slot Bragg grating structure for small electric field detection

In this paper, we present an ultra-compact 1D photonic crystal(Ph C) Bragg grating design on a thin film lithium niobate slot waveguide(SWG) via 2D-and 3D-FDTD simulations. 2D-FDTD simulations are employed to tune the photonic bandgap(PBG) size, PBG center, cavity resonance wavelength, and the whole size of Ph C. 3DFDTD simulations are carried out to model the real structure by varying different geometrical parameters such as SWG height and Ph C size. A moderate resonance quality factor Q of about 300 is achieved with a Ph C size of only 0.5 μm× 0.7 μm× 6 μm. The proposed slot Bragg grating structure is then exploited as an electric field(E-field) sensor. The sensitivity is analyzed by 3D-FDTD simulations with a minimum detectable E-field as small as 23 m V∕m. The possible fabrication process of the proposed structure is also discussed. The compact size of the proposed slot Bragg grating structure may have applications in on-chip E-field sensing, optical filtering, etc.

Resonance-assisted light–control–light characteristics of SnS_2 on a microfiber knot resonator with fast response

An all-optical light–control–light functionality with the structure of a microfiber knot resonator (MKR) coated with tin disulfide (SnS_2) nanosheets is experimentally demonstrated. The evanescent light in the MKR [with a resonance Q of ～59,000 and an extinction ratio (ER) of ～26 dB] is exploited to enhance light–matter interaction by coating a two-dimensional material SnS_2 nanosheet onto it. Thanks to the enhanced light–matter interaction and the strong absorption property of SnS_2, the transmitted optical power can be tuned quasi-linearly with an external violet pump light power, where a transmitted optical power variation rate ΔT with respect to the violet light power of ～0.22 dB∕mW is obtained. In addition, the MKR structure possessing multiple resonances enables a direct experimental demonstration of the relationship between resonance properties (such as Q and ER), and the obtained ΔT variation rate with respect to the violet light power. It verifies experimentally that a higher resonance Q and a larger ER can lead to a higher ΔT variation rate. In terms of the operating speed, this device runs as fast as ～3.2 ms. This kind of all-optical light–control–light functional structure may find applications in future all-optical circuitry, handheld fiber sensors, etc.