纸基荧光设备：体外诊断的新廉价解决方案
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更新于2024-08-26
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本文主要探讨了用于体外诊断的纸基荧光设备在医疗系统中的重要性，特别是在疾病的早期检测、条件评估和感染监控方面。体外诊断（In Vitro Diagnostics, IVD）是现代医疗保健不可或缺的一部分，它通过非侵入性方式分析样本，帮助医生做出准确的诊断决策。然而，开发出既经济又敏感的检测方法一直是该领域面临的挑战。
纸基荧光设备作为一种新兴的低成本分析工具，利用其独特的性质，如便携性、易制备和环境友好，正在吸引越来越多的关注。这些设备通常基于纸作为基质，结合荧光标记技术，能够将生物分子的相互作用转化为可见的荧光信号，从而实现对目标分子的定量或定性检测。这种技术特别适用于POC（Point-of-Care）检测，即在患者身边进行快速、即时的诊断，无需专门的实验室设施。
文章作者Meirong Wang、Qiongyu Lai、Qiang Jua、Lin Li、Hai-Dong Yu 和 Wei Huang等人来自南京科技大学和南京邮电大学的研究团队，他们深入研究了纸基荧光设备的设计原理、制造过程、敏感度优化以及应用在各种生物检测试剂中的可能性，如生物传感器和生物电子学领域。
具体而言，研究内容可能包括以下几个关键点：
1. **纸基材料的选择与改性**：选择适合荧光反应的纸张，对其进行化学或物理改性以提高其对生物标志物的吸附和荧光信号的稳定性。
2. **荧光探针设计**：设计具有高特异性和灵敏度的荧光标记探针，以便在体外环境中有效识别和捕获目标分子。
3. **信号放大机制**：探讨如何通过设计高效的信号放大策略，如酶催化、能量转移或纳米结构增强，来提高检测限并减小背景噪音。
4. **读取和分析**：介绍纸基设备上常用的光学检测方法，如便携式荧光仪或智能手机应用程序，以及数据处理和分析算法。
5. **临床应用案例**：分享实际应用中的成功案例，展示纸基荧光设备在疾病筛查、药物监测或病原体检测等方面的有效性。
6. **未来发展与挑战**：讨论纸基荧光设备可能面临的挑战，如长期稳定性、标准化和法规要求，以及如何通过技术创新克服这些问题。
这篇研究论文为体外诊断领域提供了一个有价值的视角，强调了纸基荧光设备在提升诊断效率和降低成本方面的潜力，对于推进POC诊断技术的发展具有重要意义。
and broad emission bands. And fluorescent dyes used as indicators in
paper-based devices are required to change colors or be quenched after
adding analytes, and especially the complexity of the synthesis and
purification of organic molecules.
2.2. Quantum dots
Quantum dots (QDs) are highly fluorescent inorganic semi-
conductor nanocrystals in zero dimension with a diameter ranging from
2to10nm(Fig. 3a) (Chan and Nie, 1998). The QDs consist of hundreds
to thousands of atoms from group II-VI (e.g., CdSe and CdTe), group III-
V (e.g., InP and InAs), or group IV-VI (e.g., PbSe). The surface-naked
QDs usually show low fluorescence quantum yield, mainly induced by
the presence of surface defects. To address this issue, QDs with the core-
shell configuration (three types as shown in Fig. 3b) and molecules
coating become attractive in deactivating the surface trap state. QDs of
type 1 with a higher band gap, energy gap between the conduction
band (CB) and valence band (VB), as the shell and lower band gap as
the core tend to concentrate carriers within the core. Type 2 is just the
opposite. Type 3 means the CB or VB of the core within the band gap of
the shell (Stanisavljevic et al., 2015). Different from fluorophores, an
electron of QDs will be excited from the VB to the CB generating a hole
in VB and forming an electron-hole pair after absorption of a photon.
The recombination of electron-hole pairs will produce fluorescence.
The QDs have broad excitation band, symmetric emission spectra,
narrow defined tunable emission peak, long fluorescence lifetime, and
large Stokes' shifts (Zhou et al., 2005). Various colors are available by
changing the size, shape, and composition of the QDs. These char-
acteristics allow QDs to be a great alternative for paper-based diag-
nostics to detect ions (Wang et al., 2015b), nucleic acids (Duran et al.,
2016), proteins (Li et al., 2016), cells (Liang et al., 2016a), etc.
a
400 500 600
Wavelength(nm)
Emission
Absorption
Fig. 1. (a) Absorption and emission spectra of Rhodamine showing the Stokes' shift. (b)
Jablonski diagram showing the energy level of a generic molecule and the generation of
fluorescence (Noomnarm and Clegg, 2009).
Table 1
Comparison of different fluorescent materials used in the paper-based fluorogenic devices.
Fluorescent materials Advantages Disadvantages Applications
Fluorescent dyes a) Small size
b) Easy surface modifications
c) Good biocompatibility
a) Low fluorescence quantum yield
b) Instable fluorescence and rapid
photobleaching
c) Autofluorescence
d) Light scattering
Neisseria meningitides (Dou et al., 2014), Single-stranded DNA
(Scida et al., 2013), β-D-galactosidase (Thom et al., 2014),
Adrafinil (Caglayan et al., 2016), Alkaline phosphatase (Koo et al.,
2014), Polyols (Ikeda et al., 2012), Al
3+
(Kim et al., 2015), Heavy
metals (Feng et al., 2013), Nitroaromatic explosive (Taudte et al.,
2013), Ammonia gas (Lin et al., 2015), Hypochlorite (Lee et al.,
2015)
Quantum dots a) High quantum yield
b) Stable fluorescence
c) High Stoke shift
d) Tunable emission wavelength and
narrow emission spectra
a) Toxicity
b) Optical blinking
c) Light scattering
d) Low light penetration
Staphylococcus aureus (Chandan et al., 2016), Nucleic acid
hybridization (Noor and Krull, 2014), Nitrated ceruloplasmin (Li
et al., 2010), Cysteine and homocysteine (Wang et al., 2015a),
Tyrosinase (Yan et al., 2015), Peptides (Petryayeva and Algar,
2013), Liver cancer cell (Wu et al., 2015), H
2
O
2
(Duran et al.,
2016), Cu
2+
(Wang et al., 2015b), Nitroaromatic explosive (Zhang
et al., 2011), Methyl viologen (Su et al., 2015b)
Metal nanoclusters a) Tunable and strong fluorescence
emission
b) Small size
c) Non-toxicity and biocompatibility
a) Difficulties to obtain
monodispersed metal clusters
Rifampicin (Chatterjee et al., 2015), Organophosphate (Zhang
et al., 2014), Cu
2+
(Liu et al., 2012), Hg
2+
(Qi et al., 2015),
Nitroaromatic explosive (Ma et al., 2012)
Upconversion
nanoparticals
a) High photostability and quantum
yield
b) Zero auto-fluorescence background
for the improved signal-to-noise ratio
c) Large anti-stokes shifts
d) Multicolor-emission capability
e) Biocompatibility
a) Near-infrared light with high
density as the excitation resource
Nucleic acid hybridization (Ju et al., 2014; Noor and Krull, 2013),
Multiple cancer (Xu et al., 2016)
Carbon dots a) Strong fluorescence
b) Low toxicity and good
biocompatibility
c) Good water solubility
d) Tunable emission
e) Easy functionalization
a) The uncertain origins of
fluorescent emission
Copper ions (Wang et al., 2016); Pb
2+
(Abhishek et al., 2016);
Al
3+
(Kim et al., 2015); Hg
2+
( Zou et al., 2016; Yuan et al., 2013);
DNA (Wang et al., 2013); HIV (Kurdekar et al., 2016)
M. Wu et al.
Biosensors and Bioelectronics 102 (2018) 256–266
258
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