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化学进展 2023, Vol. 35 Issue (12): 1793-1806 DOI: 10.7536/PC230410 前一篇   后一篇

• 综述 •

RIfS干涉基底的制备、应用及展望

苏倩倩1,*(), 孙宇1, 张文文1, 彭正得1, 钱卫平2   

  1. 1 江苏海洋大学药学院 连云港 222005
    2 东南大学生物电子学国家重点实验室 南京 210096
  • 收稿日期:2023-04-10 修回日期:2023-09-10 出版日期:2023-12-24 发布日期:2023-11-30
  • 作者简介:

    苏倩倩 博士,硕士生导师。主要研究方向为生物传感和生化分析。主要研究工作包括:(1)有序多孔纳米材料的制备及性能研究;(2)基于有序多孔纳米材料的生物传感器的研制;(3)生物传感器在药物分析及新药筛选中的应用。作为第一作者在Anal. Chem.、ACS Appl. Mater. Interfaces等期刊上发表多篇论文,获PCT国际发明专利授权1项、中国发明专利授权1项、实用新型专利授权1项。2021年获得江苏省“双创博士”人才基金资助。

  • 基金资助:
    数字医学工程全国重点实验室开放研究基金资助课题(2023-K13); 江苏省“双创博士”人才基金项目(JSSCBS20211301); 江苏海洋大学博士科研启动项目(KQ21002)
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Preparation, Application and Prospect of RIfS Interference Substrates

Qianqian Su1,*(), Yu Sun1, Wenwen Zhang1, Zhengde Peng1, Weiping Qian2   

  1. 1 Pharmacy School, Jiangsu Ocean University,Lianyungang 222005, China
    2 State Key Laboratory of Bioelectronics, Southeast University, Nanjing 210096, China
  • Received:2023-04-10 Revised:2023-09-10 Online:2023-12-24 Published:2023-11-30
  • Contact: *e-mail: suqianqian@jou.edu.cn
  • Supported by:
    Open Research Fund of State Key Laboratory ofDigital Medical Engineering(2023-K13); Shuangchuang Ph.D award of Jiangsu province(JSSCBS20211301); Doctoral research project of Jiangsu Ocean University(KQ21002)

反射干涉光谱(Reflectometric interference spectroscopy,RIfS)是一种利用白光干涉原理来对薄膜光学厚度进行测量的非标记检测技术。干涉基底作为RIfS系统的传感单元,是RIfS技术的核心部分,也是决定RIfS系统性能的关键。目前使用的干涉基底通常被分为两大类:一类是以无机氧化物或聚合物薄膜为代表的平面固体基底,另一类是以多孔硅(pSi)、纳米多孔阳极氧化铝(NAA)以及二氧化硅胶体晶体(SCC)为代表的多孔基底。平面固体基底制备简单且信号稳定,但是检测灵敏度通常比较低;多孔基底具有较大的比表面积,可以捕获更多待测分子,因此与平面固体基底相比检测灵敏度有所提高,并且具有更多的调节空间,非常适合生化传感平台的开发。从pSi到NAA再到SCC,多孔基底制备的可控性及传感性能不断提高,成为RIfS干涉基底的发展方向。本文对RIfS干涉基底发展现状进行了总结和讨论,阐述了基底的常用制备方法,总结了其在生物传感领域代表性的应用,重点讨论了不同基底的优缺点,并对干涉基底未来的发展进行了展望。

关键词： 反射干涉光谱, 干涉基底, 纳米多孔阳极氧化铝, 多孔硅, 胶体晶体

Reflectometric interference spectroscopy (RIfS) is a label-free detection technique by measuring the optical thickness of thin films which is based on white light interference. Interference effective substrates, as the sensor unit of the RIfS system, the construction of which is the core part of RIfS technology and the key to determining the performance of the RIfS system. Currently used interference substrates are generally divided into two categories: one is the planar solid substrates represented by inorganic oxides or polymer films, and the other is the porous substrates represented by porous silicon (pSi), nanoporous anodic alumina (NAA) and silica colloidal crystals (SCC). The preparation of planar solid substrate is simple and the signal is stable, but the detection sensitivity is usually low. In comparison with planar solid substrates, a porous substrate can provide a three-dimensional structure with a large specific surface area which will result in increased ligand immobilization density and capture of analyte. Therefore, the detection sensitivity is improved and there is more room for adjustment, which is very suitable for the development of a biochemical sensing platform. From pSi to NAA to SCC, the preparation controllability and sensing performance of porous substrates are continuously improved, which is considered a promising development direction of RIfS interference substrate. Here, the research status of RIfS interference substrates has been summarized and discussed, the common preparation methods of substrates are described, their representative applications in biosensing are summarized, the advantages and disadvantages of different substrates are discussed, and the future development directions of RIfS interference substrates has also been outlined.

Contents

1 Introduction

2 Measurement principles of reflectometric interference spectroscopy

3 Interference substrate

3.1 Planar solid substrate

3.2 Porous silicon substrate

3.3 Nanoporous anodic alumina substrate

3.4 Silica colloidal crystals substrate

4 Conclusion and outlook

Key words: reflectometric interference spectroscopy, interference substrate, nanoporous anodic alumina, porous silicon, colloidal crystal
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图1 反射干涉光谱测量原理图
Fig. 1 Schematic diagram of reflectometric interference spectroscopy
图2 多孔硅基底的侧面SEM图[36]
Fig. 2 The SEM image of the side view of porous silicon substrate[36]
表1 基于多孔硅基底的生物传感应用举例[59]
Table 1 Examples of biosensors based on porous silicon substrates[59]
Analyte under analysis Probe molecule Detection range Limit of detection Response time(min)
DNA (15 mer) ssDNA 1~10 nmol/L 1 nmol/L 20
Subtilisin Gelatin 0.37~370 nmol/L 370 pmol/L 20
Sortase-A Fluorogenic peptide 4.6~46 000 pmol/L 0.08 pmol/L 30
Sheep IgG Protein A 10~500 μg/mL 0.6 μg/mL 90
Bacteria (E. coli) Peptide 103~105 cells/mL 103 cells/mL 60
Streptavidin Biotin 0.5~5 μmol/L 0.5 μmol/L 20
Vancomycin Peptide 0.005~0.1 mg/mL 5 μg/mL 20
图3 (a) 纳米孔阳极氧化铝基底的结构示意图;(b) 纳米孔阳极氧化铝基底的正面及侧面SEM图(图中标尺分别为400和250 nm);(c) 纳米孔阳极氧化铝基底的制备装置示意图[65]
Fig. 3 (a) Illustrative scheme describing the most representative geometric features of nanoporous anodic alumina (NAA); (b) top and cross-section scanning electron microscopy (SEM) images of NAA (scale bars = 400 and 250 nm, respectively); (c) illustration describing a basic electrochemical anodisation cell used to produce NAA[65]
图4 基于NAA基底的RIfS传感系统的构造示意图[77]
Fig. 4 Schematic diagram of RIfS sensing system based on NAA substrate[77]
表2 胶体晶体的常用制备方法[101]
Table 2 Common preparation methods of colloidal crystals[101]
Method Remarks
Drop casting
(Sedimentation)		 Simple but slow process.
Patches of colloidal crystals formed.
Difficult to control exact conditions
Centrifugation Simple and fast process.
Generally big bulky colloidal crystals formed.
Spin-coating Simple and fast process.
Monolayer formation possible. Patches of small coating area of monolayers.
Dip-coating Can control thickness of layers by the speed of withdrawal.
Gradient in layer thickness.
Shear ordering Requires very good control of process parameters.
Slow process. Makes thin films.
Langmuir-Blodgett Monolayer compressed on water surface by mobile arms.
Short range order of closed packed regions within the monolayer.
Monolayer transfer onto substrate can be repeated to deposit multilayers exactly as desired.
Takes time for preparation of equipment and spreading of particles.
Direct assembly on water surface Simple and fast process.
Good two-dimensional closed pack array on water surface.
One monolayer at a time can be transferred.
Can be repeated to deposit multilayers exactly as desired.
Magnetic self-assembly Requires highly-charged monodisperse magnetic colloidal particles.
Self-assembly occurs inside liquid medium.
Can be controlled by external magnetic field.
Vertical deposition Requires very good control of evaporation conditions (i.e., temperature and humidity) for a good deposition.
Slow process (days).
Very good quality of colloidal crystals formed under the proper conditions.
Gradient in the thickness of colloidal crystal formed.
图5 基于硅胶晶体薄膜的反射干涉传感器原理图[100]
Fig. 5 Schematic diagram of the reflectometric interference sensor based on silica colloidal crystal films[100]
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摘要

RIfS干涉基底的制备、应用及展望