基于太赫兹时域光谱技术的磺胺甲噁唑多晶型现象

磺胺甲噁唑(SMX)作为典型的一类光谱抗生素,经常被用于敏感菌引起的各类感染。由于其晶体内部结构的不同,SMX 将以两种不同的多晶型形式存在。不同晶型常常具有不同的物理化学性质,这些差异可能会对药物的流动性、稳定性以及药效等有较大影响。新兴发展起来的太赫兹光谱技术对于分子间弱的相互作用及大分子的骨架振动、偶极子的旋转和振动跃迁以及晶体中晶格的低频振动吸收都非常敏感,在药物以及生物等领域获得了重要的应用。利用太赫兹时域光谱(THz-TDS)技术在室温下对两种不同多晶型SMX 类药物在0.2~1.5 THz 范围内进行了光谱测量,得到对应的吸收谱,发现其在太赫兹波段都有明显的特征吸收峰,可作为其指纹谱用于该类药物多晶型的识别。不同温度下(95~296 K)获得太赫兹时域波形以及对应的频域吸收谱图,结果发现时域波形以及频域吸收谱均与温度呈现规律变化。该研究结果表明THz-TDS 技术药物与生物领域研究、区分药物分子多晶型现象等方面具有重要的应用。     

Optical properties of selected Chinese Traditional Patent Medicines and Western Medicines terahertz range

The spectral characteristics of Sang Ju Gan Mao Granules, Gan Mao Jie Du Tablet, Fu Fang Jin Yin Hua Granules and Compound Paracetamol, and Amantadine Hydrochloride Tablets are studied by terahertz time-domain spectroscopy (THz-TDS) technologies in the spectral range of 0.2—1.7 THz. The absorption spectra and the indexes of refraction are obtained. It can be seen that the three samples of Chinese Traditional Patent Medicines have almost the same absorption peaks at 1.44 THz. However, the absorption peaks of the three western medicine samples are at 0.73, 1.01, and 1.18 THz, respectively. The large spectral differences between different drugs are strong evidences that THz time-domain spectroscopy is a useful fingerprint technique in the study of pharmaceutical compounds and the crack down on the fake medicines.     

葡萄糖溶液的太赫兹光谱观察

生物有机分子的生物功能必须在其水溶液中实现。太赫兹波对水非常敏感,太赫兹时域光谱(THz-TDS)技术能够检测生物分子——水分子界面的集体水分子网络动力学变化,是检测和研究生物有机分子溶液的理想工具。本文利用太赫兹时域光谱技术研究了葡萄糖的分子结构,获得葡萄糖及其不同浓度的溶液在室温氮气环境下的太赫兹时域吸收光谱,以及在室温真空环境下的傅里叶远红外光谱(FTFIR)。结果表明葡萄糖溶液对太赫兹波有特征吸收峰,不同浓度的葡萄糖溶液对太赫兹波的吸收各不相同。故使用太赫兹时域光谱技术能够完成葡萄糖及其不同浓度溶液的鉴别。     

In-Situ Measurement of Vitamin C Content in Commercial Tablet Products by Terahertz Time-Domain

Terahertz time-domain spectroscopy (THz-TDS) was applied to investigate the feasibility of in-situ measuring vitamin C content in commercial tablet products without any pretreatments. Characteristic absorption peaks of vitamin C were analyzed with quantum mechanical calculation to reveal the molecular origin of them. The peak appearing at 1.08 THz was then selected and tested for its suitability as a fingerprint signal for analyzing the vitamin C content in dietary supplement tablets. There are a couple of factors influencing THz absorbance other than concentration. Among those, the effects of tablet thickness and types of excipients in the tablet products were found to be significant, and were corrected with the calibration curve to determine vitamin C concentration in tablet forms. Furthermore, commercial tablet products in the market were analyzed using THz-TDS and the measured vitamin C contents were in good agreement with those determined using a reference method (high-performance liquid chromatography). Thus, our results suggest that THz-TDS can be used for the in-situ analysis of vitamin C in commercial tablet products.     

基于多特征联合的太赫兹药品检测方法

以药品为研究对象,利用太赫兹时域光谱系统对3种不同药品进行测量并提取折射率、介电常数和物质因子等多个特征参数,然后联合多个特征参数作为输入,采用后向传播(BP)神经网络、支持向量机(SVM)和学习矢量化(LVQ)3种机器学习方法分别对药品进行多特征联合检测分类识别。实验结果表明,多特征联合检测方法识别准确率能够达到95%以上,有效提高药品的检测分类准确度,可用于药品的检测和分类识别。     

Monitoring PM2.5 in the Atmosphere by Using Terahertz Time-Domain Spectroscopy

The real-time monitoring of the air pollution with multiple sources is of great significance for pollution control and environmental protection. In this paper, we presented a study of terahertz time-domain spectroscopy (THz-TDS) as a direct tool for monitoring the component and content of PM2.5 in atmosphere. Due to the THz absorption, the intensities of the peaks in THz-TDS decreased with the augment of PM2.5 and were proportional to the PM2.5 content. The ratio of absorbance A to PM2.5 reflected a basically unchanged tendency, indicating the little change of principal elements under the pollution degree. In the high-pollution condition, a lot of SO₂ from vehicle and factory was emitted into air. The elements, such as S and O from anions, had a stronger absorption effect in THz range. Based on the absorbance spectra, the absorption tendencies with PM2.5 over the whole range were validated by principal component analysis and the quantitative model with a high correlation was built by using back propagation artificial neural network. BPANN model improved the precision of linear fitting between peak intensities and PM2.5. The research demonstrates that THz-TDS is a promising tool for fast, direct, and reliable monitoring in environmental applications.     

太赫兹时域光谱技术用于准确快速地提取薄片的光学参数

由于太赫兹辐射能量低并且脉冲宽度窄（皮秒量级）,太赫兹时域光谱技术作为一种提取材料光学参数的新兴光谱分析手段具有无损伤和高时间分辨率的特点。法布里-珀罗震荡是透射模式太赫兹时域光谱提取薄片的光学参数的主要障碍。为了即时地滤除法布里-珀罗震荡以获得薄片准确的光学参数提出了一种可靠的方法。该方法为每一片测量样品实时地设计其独有的带阻滤波器以滤除叠加在折射率和吸收系数的初始值中的法布里-珀罗震荡。同时不同掺杂的硅片和氨基酸薄片的实验结果证实了该方法的可行性。     

On the Correlation of Effective Terahertz Refractive Index and Average Surface Roughness of Pharmaceutical Tablets

In this paper, we have studied terahertz (THz) pulse time delay of porous pharmaceutical microcrystalline compacts and also pharmaceutical tablets that contain indomethacin (painkiller) as an active pharmaceutical ingredient (API) and microcrystalline cellulose as the matrix of the tablet. The porosity of a pharmaceutical tablet is important because it affects the release of drug substance. In addition, surface roughness of the tablet has much importance regarding dissolution of the tablet and hence the rate of drug release. Here, we show, using a training set of tablets containing API and with a priori known tablet’s quality parameters, that the effective refractive index (obtained from THz time delay data) of such porous tablets correlates with the average surface roughness of a tablet. Hence, THz pulse time delay measurement in the transmission mode provides information on both porosity and the average surface roughness of a compact. This is demonstrated for two different sets of pharmaceutical tablets having different porosity and average surface roughness values.     

碳类烟幕材料对太赫兹波的衰减特性

为获得太赫兹波对碳类烟幕的穿透特性,采用压片法分别将不同比例混合的石墨粉和KBr、碳黑粉和KBr进行压片,利用太赫兹时域光谱仪在0.2~1.1 THz频率范围内测试压片样品的太赫兹透射光谱,进而获得样品在该频率范围内的吸收系数。研究发现:随着频率的增大,样品的吸收系数均逐渐增大,且在同一频率处,其均随碳类粉末掺杂比例的增加而增大;与石墨相比,相同掺杂比例的碳黑样品具有更大的吸收系数。结果表明,太赫兹波具有较强的穿透石墨烟幕的能力,但其对碳黑烟幕的穿透能力较弱,利用碳黑有望进行太赫兹波段烟幕的研制。     

二硝基苯甲酸同分异构体的太赫兹与红外光谱特性

利用太赫兹时域光谱系统(THz-TDS)和傅里叶变换红外光谱仪(FTIR)分别研究了2,4-, 2,5-, 3,4-, 3,5-二硝基苯甲酸的吸收谱.实验结果表明, 4种同分异构体的吸收光谱在红外波段(1 400~1 800 cm-1)表现出相似性, 而在太赫兹波段(0.3~2.2 THz)却存在非常明显的区别.利用密度泛函理论(DFT)对4种物质的吸收频谱进行计算, 并根据计算结果对吸收光谱的相似性和差异性进行解释.太赫兹时域光谱技术为鉴别物质的同分异构体提供了一种可行的手段.     

Fundamentals of Measurement in Terahertz Time-Domain Spectroscopy

Terahertz time-domain spectroscopy (THz-TDS) has emerged as a main spectroscopic modality to fill the frequency range between a few hundred gigahertz to a few terahertz. This spectrum has been known as “terahertz gap” owing to limited accessibility by conventional electronic and optical techniques. Over the past two decades, THz-TDS has evolved substantially with enhanced compactness and stability. Since THz-TDS is becoming an industrial standard, the performance and precision of the system are of prime importance. This article provides an overview on terahertz metrology, including parameter estimation, signal processing, measurement characteristics, uncertainties, and calibrations. The overview serves as guidance for metrology and further developments of THz-TDS systems.     

鞣花酸的太赫兹光谱研究

鞣花酸是一种存在于多种植物中的天然多酚组分,近年来越来越多的实验证实鞣花酸在抑制癌细胞增长和诱导癌细胞凋亡方面有很好的效果,同时也具有抗氧化和抗辐射等作用,在抗癌药品及保健药品中占有重要地位。因此对鞣花酸的研究有着重要的意义。太赫兹时域光谱技术（THz－TDS）是一种新型的时间分辨相干探测技术,本文利用太赫兹时域光谱技术研究了鞣花酸在0.2－2.4THz波段的光谱特性,得到了鞣花酸的吸收谱和折射率谱,并利用密度泛函理论(DFT)进行了模拟计算。研究发现,鞣花酸在该波段有光谱响应,分别在0.44、0.73、0.99、1.26、1.58、1.87和2.19THz频率处出现了反常色散现象和吸收峰。可以作为检测鞣花酸存在的定量分析依据,为药品及食品检测提供指导。     

硫酸软骨素掺假鉴定的太赫兹和红外光谱对比

研究太赫兹时域光谱(Terahertz Time-domain Spectroscopy,THz-TDS)技术和红外光谱技术用于硫酸软骨素掺假鉴定的可行性.将六偏磷酸钠混入鲨鱼硫酸软骨素中的样品作为掺假研究对象,利用上述两种技术对样品进行对比研究.研究发现,THz光谱和红外光谱谱图中六偏磷酸钠标样、鲨鱼硫酸软骨素标样与掺假(混合)样品谱线均表现出较明显的差异,可用于鉴别鲨鱼硫酸软骨素的六偏磷酸钠掺假.实验结果表明,此两种技术能够鉴别的六偏磷酸钠:鲨鱼硫酸软骨素最低质量比分别为1:15和1:1,THz-TDS表现出较为灵敏的检测性能;综合考虑,THz-TDS技术可以比较好的用于鲨鱼硫酸软骨素的六偏磷酸钠掺假检测.本工作为发展一种基于THz-TDS技术的准确、快速和无损鉴别鲨鱼硫酸软骨素掺假的新型光谱技术奠定了前期实验基础.     

Amplitude Calibration in Terahertz Time-Domain Spectroscopy Using Attenuation Standards

An amplitude calibration method for a terahertz time-domain spectroscopy system (THz-TDS) is proposed and demonstrated for transmittance measurement. The method is based on a direct comparison method using a terahertz attenuator as a reference standard. The measurement uncertainties of the THz-TDS are evaluated in transmittance measurements of metalized film attenuators as test samples. The relative expanded uncertainty is found to be 6.4–14.0% (k = 2) at 1 THz for transmittances ranging from 1 to 0.001. In addition, the calibration capability is extended to the available frequency range of the THz-TDS by considering spectral flatness of the reference standard. Validations of the method are also conducted by comparing the measurements between different systems, and it is confirmed that they agree well with each other.     

盐酸吗啡的太赫兹光谱和理论仿真分析

采用太赫兹时域光谱(THz-TDS)技术测量了盐酸吗啡原料药、4种辅料、中间体、成药在0.2～2 THz波段的光谱.盐酸吗啡原料药特征吸收峰为0.75 THz,1.17 THz,1.76 THz,原料药到成药的THz光谱发生了改变,中间体和成药的吸收谱有非常高的一致性,说明包衣对成药的THz光谱没有显著影响.采用密度泛...     

Uncertainty in Terahertz Time-Domain Spectroscopy Measurement of Liquids

Terahertz time-domain spectroscopy (THz-TDS) is a significant technique for characterizing materials as it allows fast and broadband measurement of optical constants in the THz regime. The measurement precision of the constants is highly influenced by the complicated measurement procedure and data processing. Taking THz transmission measurement of liquids into account, the sources of error existing in THz-TDS process are identified. The contributions of each source to the uncertainty of optical constants in THz-TDS process are formulated, with particular emphasis on the effect of multilayer reflections and plane wave assumption. As a consequence, an analytical model is proposed for uncertainty evaluation in a THz-TDS measurement of liquids. An actual experiment with a Di 2-Ethyl Hexyl Phthalate (DEHP) sample is carried out to show that the proposed model could be a basis to evaluate the measurement precision of optical constants of liquids.     

基于太赫兹时域光谱技术的农药残留检测方法

太赫兹时域光谱(THz-TDS)技术是近年来涌现出来的崭新的光谱测量新技术.本研究提出了一种基于THz-TDS技术农药残留检测方法,并以灭多威和乙氧氟草醚两种农药作为实验介质证明此方法的可行性.应用太赫兹时域光谱系统测得了这两种农药的时域光谱信号,利用基于菲涅尔公式的数据处理模型得到了它们在THz波段的折射率谱和吸收系数谱.从实验结果可以看出两种农药在0.2~2.0THz范围内存在明显的特征吸收峰,且差别很大.经分析认为这些吸收峰是由分子的集体振动模式以及分子间相互作用引起,它们是农药分子的指纹吸收光谱,可以应用于分子识别中.本研究证明了THz-TDS技术应用于农药残留检测的可行性,表明其在农药残留检测中具有潜在的应用价值.     

太赫兹扫描成像在高通量测量铜合金薄膜电导中的应用（特邀）

高通量制备与表征对将材料基因组方法应用于先进材料研发制造实践起着关键作用。针对基于材料基因工程的高通量实验技术应用,采用透射式太赫兹扫描成像方法,对样品密度为144个/片的铜合金薄膜材料芯片进行了高通量电导的快速、微区检测。基于Tinkham薄膜透射方程及Fresnel公式的太赫兹光谱成像表征技术,对不同组分含量铜合金薄膜的太赫兹测量结果与四探针测量数据比较,具有一致的趋势。通过太赫兹成像可以进行同一基底上 144个高通量组合铜合金样品点电导的半定量比较。对代表性样品点的电导变化趋势与合金组分含量变化趋势,以及微观组织形貌进行分析比较得到相关对应关系,显示出太赫兹检测方法用于微区高通量金属薄膜电导表征方面的巨大潜力,显著提升研发效率。     

THz-TDS信号的相似性度量及其应用

太赫兹(Terahertz, 简称THz)波段位于微波和红外线之间,属于远红外线和亚毫米波范畴。太赫兹时域光谱(Terahertz time domain spectroscopy,简称THz-TDS)信号脉冲具有宽频带特性,其中蕴含了丰富的信息,但同时也给THz-TDS信号的分析和处理带来了困难。太赫兹时域光谱信号的处理和分析还处于起步阶段。基于几何代数理论,本文首先将在频率域上的THz-TDS信号表达为高维实矢量空间中的矢量,并对这些矢量使用几何代数中的超复数来进行描述。针对THz-TDS信号的特点,本文引入矢量外积定义了THz信号矢量的相似性函数,以此来度量THz信号的差异。同时本文还使用几何代数语言定义了矢量间的欧几里德距离,并且分别推导欧氏距离和相似性函数的具体计算方法。最后,本文具体地将这两种度量应用于THz-TDS信号的分类和辨识中,并和传统的欧氏距离进行了对比实验。本文给出的实验验证了这两种度量的可行性和有效性,并且表明本文提出的相似性函数相比于欧氏距离具有更好的抗干扰能力;特别的,在待辨识的物质种类较多和信号集波形出现混杂的情况下,本文提出的信号矢量间相似性函数能更好地度量THz信号之间的差异。      

基于太赫兹光谱的页岩有机质定量分析

页岩是油气储层的主要类型之一,其微量有机质的准确表征是油气资源勘探中的一大热点和难点。利用太赫兹时域光谱技术(THz-TDS)对不同原油含量(ppm级)的页岩进行测试与分析,结果表明,太赫兹光谱响应与页岩有机质含量存在单调关系：随着原油浓度增加,单位厚度太赫兹时域光谱幅值衰减系数线性增加。结合有效介质理论,确定了太赫兹介电常数与200 ppm以下原油含量之间的线性关系。研究表明,太赫兹时域光谱技术可作为页岩中微量原油表征的有效方法,对提高油气资源勘探效率具有重要意义。