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材料导报  2019, Vol. 33 Issue (1): 48-55    https://doi.org/10.11896/cldb.201901005
  生物医学工程领域的高技术关键材料 |
基于荧光法纸基器件在体外疾病检测中的应用进展
吴美容, 赖琼宇, 周佳, 倪赟, 吴琼, 张承武, 于海东, 李林
南京工业大学先进材料研究院,南京 210009
Progress of in Vitro Diagnostics by Fluorescent Assay on Paper-based Devices
WU Meirong, LAI Qiongyu, ZHOU Jia, NI Yun, WU Qiong, ZHANG Chengwu, YU Haidong, LI Lin
Institute of Advanced Materials (IAM), Nanjing Tech University, Nanjing 210009
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摘要 在发展中国家的贫困地区,由于缺乏医疗设备,很多疾病的诊断只能依靠医疗工作者根据病人的症状进行估诊,往往延误了治疗。每年仍有多达五亿的疟疾患者由于未显示出病症而没能在感染早期被诊断出来,导致更多人被传染。因此,这些地区的居民亟需操作简单、廉价实用、可随身携带、无需辅助器材(如电、泵、光学器件等)的纸基器件检测常见疾病。纸基器件常用的检测方法有比色法、荧光法、化学发光法、电化学法、电化学发光法等。不同的检测方法可实现疾病的早期诊断以及食品质量检测和环境监测。因此,纸基器件的高检测速率、高选择性、高灵敏性,以及相对较低的成本和无污染优势,使其受到体外检测及相关应用检测的青睐。
   然而,纸基器件检测仍存在一些问题,尚待突破。例如,如何提高纸基器件检测的多样性、稳定性、重复性以及检测设备的便携性等。在不同的检测方法中比色法是最直观、最常用的一种方法,该方法通过显色反应,利用肉眼观察进行半定量分析,但通常会因为检测者的视觉感官不同而产生误差。该方法的局限性在于易受光线的影响,灵敏度和选择性不及电化学法。荧光法的选择性好、检出限低,但是在检测器件的便携性上还有很大的发展空间。化学发光法、电化学法以及电化学发光法在检测灵敏性、选择性上有一定的优势,但是限于电极易污染以及背景信燥比高等原因不能得到广泛应用。因此,近年来,除了对纸基器件的材料性质和器件性能有所研究外,研究者在高通量快速检测多种疾病检测应用中也取得了较好的成果。
   本文归纳了建立在荧光纸基器件方法上的发展应用,分别对荧光材料包括有机染料、量子点、金属纳米簇、上转换纳米颗粒、碳点等进行介绍,举例说明其在体外检测中的应用。例如,核酸检测、蛋白检测、细胞检测等,同时也指出了其在应用中的不足。因此,设计新型的稳定型、高量子产率、抗漂白性、低毒、生物相容性好、斯托克位移较大的光学材料,需要更多研究者的参与。最后,本文展望了作为疾病早期预防诊断的荧光纸基器件的应用前景。
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吴美容
赖琼宇
周佳
倪赟
吴琼
张承武
于海东
李林
关键词:  体外诊断  纸基器件  荧光法  即时诊断  核酸检测  细胞检测    
Abstract: In poor areas of the developing countries, many diseases are delayed for treatment due to the lack of medical equipment and professional care. There are as many as 500 million malaria patients failed to be diagnosed in the early phase of infection every year, hence leading to more people being injected. Therefore, the devices that are simple, inexpensive, convenient and portable, without the need for auxiliary equipment (such as electricity, pumps, optical devices, etc.) are of urgent need for these areas to detect common diseases. Commonly used detection methods for paper-based devices include colorimetry, electrochemistry, chemiluminescence, electrochemiluminescence. The paper-based devices can be adopted in the early detection of diseases, food quality control and environmental monitoring. Thus, the rapid, high selectivity, high sensitivity, and relatively low cost and pollution-free advantages of the paper-based devices make them favored by in vitro detection and related application testing.
Despite of the advantages of the paper-based devices, some challenges still remain to be solved prior to wide practical applications. For example, how to improve the diversity, stability, repeatability of the paper-based device detection, and the portability of the detection devices. Co-lorimetry is the most intuitive and commonly used detection methods, which based on the chromogenic reaction (resulting from the aggregation and/or separation of nanocrystals induced by chemical/biochemical reactions between target analytes and colorimetric probes) performs semi-quantitative analysis by visual observation, yet generally produces errors due to the visual senses of different examiners. In addition, the limitation of this method lies in its vulnerability to light, and poorer sensitivity and selectivity than that of the electrochemical methods. The fluorescence method exhibits good selectivity and low detection limit, but still have great development space in the portability of the detection devices. The electrochemistry, chemiluminescence, electrochemiluminescence have certain superiorities in detecting sensitivity and selectivity, yet the electrode pollution and high background signal-to-dry ratio of restrict their extensive application. Therefore, in recent years, researchers not only concentra-ted on the investigations of material properties and device performance, but also achieved leap-forward results in the high-throughput detection techniques.
This paper summarizes the development and application of the fluorescent detection on paper-based devices, introduces the fluorescent mate-rials including organic dyes, quantum dots, metal nanoclusters, upconverting nanoparticles, carbon dots, etc., and illustrates their application in in vitro detection, for example, nucleic acid detection, protein detection, cells detection and so on, points out their defects in the application as well. Therefore, it is imperative to design new types of optical materials with stable, high yield, anti-bleaching, low toxic, good biocompatible and large stoker displacement. Finally, this paper looks forward to the application prospects of fluorescent paper-based devices as an early diagnosis of disease prevention.
Key words:  in vitro diagnostics    paper-based devices    fluorogenic detection    instant diagnosis    nucleic acid detection    cell detection
               出版日期:  2019-01-10      发布日期:  2019-01-24
ZTFLH:  TB34  
  R-1  
基金资助: 国家自然科学基金(81672508;61505076;61601218);江苏省杰出青年基金(BK20170041)
作者简介:  吴美容, 南京工业大学先进材料研究院博士研究生,在李林教授指导下进行研究。吴琼,南京工业大学先进材料研究院副教授。李林,南京工业大学先进材料研究院教授,博士生导师, iamlli@njtech.edu.cn。
引用本文:    
吴美容, 赖琼宇, 周佳, 倪赟, 吴琼, 张承武, 于海东, 李林. 基于荧光法纸基器件在体外疾病检测中的应用进展[J]. 材料导报, 2019, 33(1): 48-55.
WU Meirong, LAI Qiongyu, ZHOU Jia, NI Yun, WU Qiong, ZHANG Chengwu, YU Haidong, LI Lin. Progress of in Vitro Diagnostics by Fluorescent Assay on Paper-based Devices. Materials Reports, 2019, 33(1): 48-55.
链接本文:  
http://www.mater-rep.com/CN/10.11896/cldb.201901005  或          http://www.mater-rep.com/CN/Y2019/V33/I1/48
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