ABSTRACT
3. Quantum Dots-Based Smart Sensing Systems
Fluorescence resonance energy transfer (FRET) is a distance-dependent physical process by which energy is transferred to non-radiative from an excited molecular fl uorophore (the donor) to another fl uorophore (the acceptor) by means of intermolecular long-range dipole–dipole coupling (Bagalkot et al. 2007). It mainly infl uenced by three factors: the distance between the donor and the acceptor, the extent of spectral overlap between the donor emission and acceptor absorption spectrum and the relative orientation of the donor emission dipole moment and acceptor absorption moment. As is required, the distance between the donor and the acceptor is smaller than a critical radius, known as the Fö rster radius.
This returns the donor to its electronic ground state, and emission may then occur from the acceptor center. QDs can be served both as FRET donors and acceptors, which have been treated in several comprehensive reviews in the recent literature. As donors, QDs can be combined with a large variety of acceptors (e.g., organic dyes or fl uorescent proteins). Using QDs as acceptors is less common because of their broad excitation spectra, which will cause QD excitation at almost any wavelength (independent of the donor). This will lead to many QD acceptors in excited states, which is very counter productive for FRET (the acceptor must be in the ground state).
The photophysical properties of QDs can be controlled by their nanocrystal core sizes, the shell thickness, and the composition of the semiconductor materials of cores and shell(s) and partly by their surface ligands (Green 2010). The superior photophysical features of semiconductor QDs (high fl uorescence quantum yields and stability against photobleaching) are usually observed in organic solvents, and their introduction into aqueous media is usually accompanied with a drastic decrease in the luminescence yields of the QDs (Gao et al. 2005). Thereafter, one of the main problems encountered in the development of QD-based systems is the modifi cation of suitable capping ligands on the surface of QDs to improve the selectivity, sensitivity and biocompatibility of these systems with enhanced brightness and stability. To address this issue, various strategies have proposed which including (a) attaching a certain metal-specifi c ligand based on an electron transfer process; (b) exchanging of the ligands with more thiol groups by host-guest chemistry on the surfaces of the particles; (c) capped the surface with amphiphilic molecules or comb like polymers possessed a hydrophilic backbone and hydrophobic side chains. As a result, QDs are intrinsically soluble in non-polar media and suitable surface modifi cation will be performed.
ions, as demonstrated by numerous works summarized in the literature (Galian and de la Guardia 2009, Frasco and Chaniotakis 2009, Callan et al.
2007). As the luminescence of QDs is very sensitive to their surface states, fl uorescence transduction is based on the principle that chemical or physical interactions occurring at the surface of the QDs, change the effi ciency of the radiative recombination, leading to photoluminescence activation or quenching.
Macrocyclic molecules with their unique structure and properties have been applied extensively, particularly in molecular recognition, materials, supramolecular self-assembly, catalysis, etc. (Miao et al. 2012, Mao et al.
2012, Mao and Li 2013, Zhao et al. 2013, Homden and Redshaw 2008).
Recently, the functionalization of nanoparticle surfaces with macrocyclic molecules in well-defi ned host-guest interactions has drawn considerable attention (Tshikhudo et al. 2005, Li et al. 2006, Sawicki and Cier 2006, Leyton et al. 2004). The combination of excellent optical properties of QDs and the molecular recognition ability of host molecules is an active line of research, which has contributed to creating sophisticated sensors based on modifying the QD surface using specifi c ligands. Here, we summarized some of recent efforts designing macrocyclic molecules-coated QDs and their application as smart fl uorescent chemosensors.
3.1 Crown-ether-Coated Quantum Dots for Fluorescence Sensing Surface modifi cation of the QDs by attaching a certain metal-specifi c ligand could be an attractive approach to achieve specifi c response of the QDs to metal ions. Crown ethers as a class of heterocyclic chemical compounds that consist of a ring containing several ether groups, is a good candidate.
Recently, based on the well-known binding ability of crown ethers to metals, crown-coated nanoparticles have been designed as selectively ion sensors (Ho et al. 2009, Lin et al. 2002, Lin et al. 2005). The most common crown ethers are oligomers of ethylene oxide, the repeating unit being ethyleneoxy, i.e., -CH2CH2O-, which strongly bind certain cations, forming stable chelation complexes (Izatt et al. 1991, Gokel et al. 2004, Rurack et al.
2000). The denticity of polyether infl uences the affi nity of the crown ether for various cations. For example, 18-crown-6 has high affi nity for potassium cations, 15-crown-5 has high affi nity for sodium cations, and 12-crown-4 has high affi nity for lithium cations. In addition, based on a sandwich complex of 15-crown-5/K+/15-crown-5, 15-crown-5 derivatives have also been reported to recognize alkali metal ions and they have the tendency to bring the donor and acceptor molecules into close proximity (Toupance et al. 1997, Flink et al. 1998, Lin et al. 2006). When one or more of the oxygen donoratoms are replaced with nitrogen atoms, aza-crown macrocyclic compounds generated. Particularly, in contrast to crown ethers, aza-crown
ethers bind the guest ions using both nitrogen and oxygen donors, and they have specifi c complex selectivity and stability for heavy or noble metal ions (Izaatl 1985, Pond et al. 2004).
By a method of ligand exchange and fl uorescence resonance energy transfer (FRET) mechanism, two different sizes (3.2 nm and 5.6 nm) of 15-crown-5 modifi ed CdSe/ZnS QDs sensors were synthesized (Fig. 3) (Chen et al. 2006). Upon addition of K+, two neighboring CdSe/ZnS QDs were bridged by a sandwich complex of 15-crown-5 and K+, which resulted in the different sized QDs coming close enough together to engage in energy transfer. In the process, QD in the size of 3.2 nm (emission at 545 nm) served as the energy donor and a 5.6 nm (emission 635 nm) particle act as the energy acceptor. Quantitative analysis was realized through a ratiometric response, the emissions at 545 nm and 635 nm decreasing and increasing respectively. This recognition scheme sparked a broad spectrum of interest to fabricate an intelligent switchable sensor due to its great versatility and fl exibility for future applications.
Figure 3. 15-Crown-5 functionalized CdSe/ZnS QDs for potassium ion recognition in a sandwich model.
Except the fl uorescence metal ion sensor based on the mechanism of energy transfer between QDs in different size, there are also fl uorescent sensor based on energy transfer between QDs and organic dyes and other nanoparticles. Recently, Lin et al. reported a ratiometric fl uorescent sensor for K+ ions based on the mechanism of fl uorescence resonance energy transfer (FRET) between the synthesized 15-crown-5-ether capped CdSe/
ZnS quantum dots and 15-crown-5-ether attached rhodamine B in pH 8.3 buffer solution (Fig. 4) (Lee et al. 2015). In this design, the synthesized
QDs (ex: 515 nm, em: 530 nm) and the crown ether attached rhodamine B (ex: 530 nm, em: 575 nm) was used as an energy donor and acceptor respectively. In the presence of potassium ions, the QD units and RhB units in aqueous solution formed the QD-RhB conjugate by the interaction between two 15-crown-5-ethers and one potassium ion. Subsequently, the fl uorescence spectra displayed a decrease at 530 nm and an increase in 575 nm respectively due to the FRET from QDs units to RhB units. The fl uorescent sensor showed high selectivity for potassium ions compared with other metal ions with a LOD of 4.3 × 10–6 M. This water soluble ratio metric sensor system can act as an excellent FRET probe for sensing applications especially in biological systems.
Kim and Park reported a fl uorescent chemosensor for metal ions composited of a pair of aza-crown ether acridinedione-functionalized quantum dots (ACEADD-QDs) and aza-crown ether acridinedione- functionalized gold nanorods (ACEADD-GNRs) (Velu et al. 2012). The ACEADD-QDs showed two emissions at 430 nm from the acridinedione moiety and 775 nm from the CdTeSe quantum dots moiety. In acetonitrile, the emission at 430 nm was suppressed due to the photoinduced electron transfer from aza-crown ether to the acridinedione moiety. Upon the presence of Ca2+ or Mg2+, the ACEADD-GNRs and ACEADD-QDs formed a sandwich complex induced by the metal ion. As a result, the near-infrared fl uorescence of QDs was quenched effectively by the gold nanoparticles due to the nanometal surface energy transfer. The fl uorescence spectra showed an increased in 430 nm and a decrease in 775 nm. The sensor displayed high selectivity towards Ca2+ and Mg2+ ions among other metal ions and provided a robust and sensitive method to detecting Ca2+ and Mg2+ with dual fl uorescence emissions.
Figure 4. Schematic illustration of FRET between crown ether modifi ed QDs and rhodamine B.
In addition, based on the mechanism of electron transfer (ET), the introduction of 1, 10-diaza-18-crown-6 to CdS:Mn/ZnS QDs has been used to specifi cally sense Cd2+ ions (Banerjee et al. 2008). The detection was based on an electron transfer process between the QDs and the ligands, and subsequent blocking of the electron transfer pathways upon exposure to Cd2+ ions owing to the complex formation between Cd2+ and 1, 10-diaza- 18-crown-6. The switching on the QD emission allowed the detection of low concentrations of Cd2+ ions. The covalent linking of aza-macrocyclic compounds (1, 4, 7-triazacyclononane, 1, 4, 7, 10-tetraazacyclododecane, and 1, 4, 8, 11-tetraazacyclo tetradecane) on the surface of QDs has resulted in the development of a new family of zinc ions nanosensors based on the similar mechanism (Ruedas-Rama and Hall 2008). Zinc ions at a concentration lower than 2.4 µM zinc ions could be detected via fl uorescence enhancement.
3.2 Porphyrin-Coated Quantum Dots for Fluorescence Sensing Porphyrins are heterocyclic macrocycles characterized by the presence of modifi ed pyrrole subunits interconnected at their α-carbon atoms via methine bridges. The existence of a variety of commercially available native and functionalized porphyrin structures makes them ideal building blocks for the design of electrochemical and optical sensing systems (Vlascici et al. 2008). Besides covalent bonding to organic QD shell, porphyrins can be linked directly to QD surface via coordination with metal atoms of the QD core/shell. Porphyrins can bind strongly to the surfaces of semiconductor substrates such as CdS and CdSe and their optical properties can be profoundly infl uenced by the presence of small gaseous molecules such as dioxygen and nitric oxide (Chrysochoos 1992, Isarov and Chrysochoos 1997, Isarov and Chrysochoos 1998, Ivanisevic and Ellis 1999). Ivanisevic and Ellis (Ivanisevic and Ellis 2000) demonstrated that fi lms of trivalent metalloporphyrins (Fe or Mn as the metal) deposited onto single-crystal CdSe substrates could serve as transducers toward oxygen with a detection limit of approximately 0.1 atm. In addition, fl uorescence quenching of CdSe QDs in the presence of trivalent metalloporphyrins, MTPPCl (TPP is tetraphenyl-porphyrin; M is Mn, Fe, Co), was developed as an NO sensor.
The electron transfer from QDs to the porphyrin’s aromatic system caused fl uorescence quenching. When NO was added to this assembly, restoration of luminescence was observed. The authors proposed that the formation of a nitrosyl adduct of metalloporphyrin caused the ligand to donate additional electron density to the bulk of the semiconductor, thereby shrinking the depletion region and enhancing the photoluminescence intensity (Ivanisevic et al. 2000). Because these changes are readily reversible, such MTPPCl fi lms have the potential to serve as online detectors for NO.
By the strategy of supramolecular assembly, a quantum dot (QD) associated to palladium (II) porphyrins have been developed to detect oxygen (O2) in organic solvents (Lemon et al. 2013). In the system, the QD acted as the two-photon antenna of NIR (700−1000 nm) excitation, and the QD emission was quenched in the presence of a surface-bound Pd porphyrin via a FRET mechanism. The insensitivity of the QD emission to O2 afforded an internal reference to establish a ratiometric O2 response.
Owing to the insensitivity of the QD to O2, a ratiometric signal transduction mechanism may be established. Because of superior spectral overlap and effi cient surface binding, the FRET effi ciency in these systems was 67−94%.
This result demonstrated that QD-palladium porphyrin conjugates may be used for oxygen sensing over physiological oxygen ranges.
Ivanisevic et al. reported the formation of nano-assemblies of CdSe/
ZnS QDs and pyridyl-substituted porphyrins. The coordination bonding of the pyridyl group with the ZnS shell of the CdSe/ZnS nanoparticles gave rise to a strong complex formation accompanied by fl uorescence quenching of CdSe/ZnS QDs. This quenching was explained partially by FRET from CdSe/ZnS nanoparticles to porphyrins (Ellis et al. 1997). Recently, a novel hybrid structure for the direct sensing of zinc ions based on CdSe QDs functionalized with tetrapyridyl-substituted porphyrin was developed by Chaniotakis’ group (Fig. 5) (Frasco et al. 2010). The pyridyl-substituted porphyrins were conjugated on the surface of CdSe QDs through one or two pyridyl nitrogen atoms, while at the same time they preserved the zinc recognition capabilities of the porphyrin, relying on the nitrogens from the pyrrole or pyridyl rings, depending on the orientation of the macrocycle.
Upon coordination with zinc ions, this porphyrin capping was shown to strongly contribute to the increase in the fl uorescence effi ciency of CdSe, via an activating interaction with the surface of the QDs. The detection limit of this nanosensor was about 0.5 µM.
Recently, Renganathan’s group reported a quantum dots–cationic porphyrin nanohybrid sensor for double stranded DNA (dsDNA) (Vaishnavi and Renganathan 2014). In this sensor, the thioglycolic acid capped CdTe QDs (CdTe-QD TGA) possessed negative charge showed strong fl uorescence. Meso-tetrakis (4-N-methylpyridyl) porphyrin (TMPyP), cationic porphyrin, was readily assembled on the surface of CdTe-QDs TGA through electrostatic interaction. The fl uorescence of CdTe-QDs was quenched drastically by the cationic porphyrin through the photoinduced electron transfer (PET) process. Upon the addition of target DNA, the fl uorescence of QDs restored sharply due to the planar cationic porphyrin intercalate or externally bind with DNA and the PET process from the QDs to porphyrin was blocked. The sensor showed high selectivity and sensitivity for double strand DNA by tracing “on-off-on” fl uorescence signals utilizing fl uorescence and synchronous fl uorescence measurements. The increasing
fl uorescence intensity was proportional to the concentration of calf thymus DNA in the range of 6.5 × 10–9 M to 29.6 × 10–8 M.
Furthermore, Patra’s group has fabricated a fluorescence switch by alloy (Cd1−xZnxS) quantum dot (QD) in the presence of porphyrin and cucurbituril (Mandal et al. 2013). The assemblies of Cd1−xZnxS QD, 5-(4-aminophenyl)-10, 15, 20-triphenyl-21 H, 23 H-porphyrin (APTPP), have been prepared by electrostatically attaching the negatively charged QD with positively charged APTPP. The drastic photoluminescence (PL) quenching and the shortening of decay time of alloy QD in the presence of porphyrin indicated the effi cient energy transfer from QD to porphyrin.
Furthermore, in the presence of cucurbituril, cucurbituril acted as a receptor to bind the porphyrin (quencher) and restored the luminescence of the QD by preventing the energy transfer from QD to porphyrin. The turn off/on fl uorescence of luminescent QD opened a new opportunity for designing a new optical-based sensor for bioapplications.
3.3 Cyclodextrins-Coated Quantum Dots for Fluorescence Sensing Expanding the applications of modifi ed QDs to develop fl uorescent sensors in water media is a topic of current interest. There have been many reports of chemical sensing of ions and small molecules with QDs by analyte- induced changes in photoluminescence. Cyclodextrins (CDs) as the most widely used macrocyclic molecule are cyclic oligosaccharides that consist of six, seven, or eight glucopyranose units in α, β, and γ forms, respectively, have attracted great interest in supramolecular chemistry (Kuwabara et al.
2002, Fragoso et al. 2002, Haider et al. 2003, Stanier et al. 2002). They are well known for forming inclusion complexes with various guest molecules because of their special molecular structure—hydrophobic internal cavity and hydrophilic external surface, which made it widely developed in
Figure 5. Porphyrin functionalized CdSe QDs for direct fl uorescent sensing of metal ions.
different sensors and separation matrices (Szejtli 1998). Since cyclodextrins are chiral, different chromatographic cyclod extrin-based chiral separation processes were accomplished. Therefore, by the method of chemical cross- link or self-assembly, cyclodextrin capped QDs can be acquired and used in different nanodevices.
Thiol groups are known to have a great affi nity to the nanoparticles surface. Thiolated cyclodextrin have been widely used in the modifi cation of metal nanoparticles (Alvarez et al. 2000, Liu et al. 1998, Nelles et al. 1996, Rojas et al. 1995). Palaniappan et al. have prepared water- soluble, perthiolated β-CD-modifi ed CdS QDs (Palaniappan et al. 2004) and monothiolated β-CD-capped CdSe/CdS QDs (Palaniappan et al.
2006) by a one-pot approach. The surface-immobilized β-CDs retain the capability of engaging molecular recognition in aqueous solutions. These receptor-modifi ed QDs have been successfully employed as a proof-of- concept system to control the analyte-induced fl uorescence change of QDs selectively and reversibly by introducing host-guest chemistry on the surface of these particles (Fig. 6). The addition of ferrocene derivatives to the system produced fl uorescence quenching by a photo-induced electron transfer mechanism, but, after the addition of adamantine molecules, a high luminescent response was observed by replacement of ferrocene with adamantine. This is an interesting example of the capability of the analytes to induce a smart controlled “on-off-on” fl uorescence switching behavior in aqueous solution. In addition, this system can also be applied to redox- active organic molecules (e.g., quinone derivatives). Benzoquinone enhances the fl uorescence, but the mechanism is still uncovered. The addition of ferrocene produced a decrease in the fl uorescence response owing to the replacement of benzoquinone molecules, which should have a high affi nity for the receptor.
Most recently, Ji and co-workers contributed an alkaline phosphatase (ALP) activity detection system based on quenching effect of the enzyme substrate and product on the β-CD-functionalized CdTe QDs (Jia et al.
2010). The CdTe QDs functionalized with GSH was covalently tethered to p-aminophenyl boronic acid (APBA). The CD units were linked to QDs via the covalently coupling between the boronic acid and secondary vicinal hydroxyl groups of the sugar units. In aqueous solution, the water- soluble β-CD and QDs exhibited highly fl uorescence in the presence of p-nitrophenyl phosphate. However, the alkaline phosphatase catalytic product, p-nitrophenol (NP), included in the cavity of β-CD quenched the fl uorescence of QDs effectively through electron transfer. The fl uorescent senor provided a simple, rapid and sensitive method for the detection of ALP activity.
By a simple and convenient sonochemical method, a water-soluble CdSe/ZnS QDs using CDs as surface-coating agents have been developed.
The formation of a tri-n-octylphosphine oxide (TOPO) complex with CD transferred QDs from organic solutions to aqueous media has been developed. The n-CD-QDs (n = α, β, γ) have a high level of emission effi ciency in aqueous solution (the quantum yields were about 27–45%).
The fl uorescence enhancement observed after the interaction of β-CD- capped QDs with polycyclic aromatic hydrocarbons (PAHs) which can be used for their analytical determination with a detection limit of 1.6 × 10–8 M (Han and Li 2008). The enhancement of the QD fl uorescence after addition
Figure 6. Cyclodextrin modifi ed QDs used for analyte sensing.