sensors Review

Recent Advances in Silicon Nanomaterial-Based Fluorescent Sensors Houyu Wang and Yao He * Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Institute of Functional Nano and Soft Materials (FUNSOM), Soochow University, Suzhou 215123, China; [email protected] * Correspondence: [email protected]; Tel.: +86-512-6588-0946 Academic Editor: Huangxian Ju Received: 5 October 2016; Accepted: 30 November 2016; Published: 3 February 2017

Abstract: During the past decades, owing to silicon nanomaterials’ unique optical properties, benign biocompatibility, and abundant surface chemistry, different dimensional silicon nanostructures have been widely employed for rationally designing and fabricating high-performance fluorescent sensors for the detection of various chemical and biological species. Among of these, zero-dimensional silicon nanoparticles (SiNPs) and one-dimensional silicon nanowires (SiNWs) are of particular interest. Herein, we focus on reviewing recent advances in silicon nanomaterials-based fluorescent sensors from a broad perspective and discuss possible future directions. Firstly, we introduce the latest achievement of zero-dimensional SiNP-based fluorescent sensors. Next, we present recent advances of one-dimensional SiNW-based fluorescent sensors. Finally, we discuss the major challenges and prospects for the development of silicon-based fluorescent sensors. Keywords: silicon nanomaterials; fluorescence; sensors

1. Introduction Rapid, sensitive, and accurate detection of chemical and biological species is of essential importance for various fields, such as biomedical diagnosis, drug screening, food safety, environmental protection, homeland and international security, among others [1–5]. Even though a number of sensors (e.g., bioassay kits) are commercially available, novel kinds of sensors with ease of portability, sufficient sensitivity, high specificity, excellent reproducibility, multiplexing detection capability, and low cost remain in high demand. Optical sensors and electrochemical sensors are commonly used sensors. The optical sensors can be divided into different types based on different detection signals, such as fluorescence, Raman, surface plasmon resonance (SPR), and so forth. Among these, fluorescent sensors with high sensitivity, short response time, easy portability, minimal equipment requirements, and low cost have attracted extensive attention [6–10]. Recently, with the significant development of optical nanomaterials, fluorescence-sensing has greatly benefited from various kinds of zero-dimensional luminescent nanoparticles. Among them, fluorescent colloidal II–VI quantum dots (QDs) have drawn much attention due to their unique optical merits, such as high photoluminescence quantum yield (PLQY), robust photostability, and sharp and tunable emission spectra, thereby allowing prolonged and multiplexed detection [11–13]. While these QD-based nanosensors are suitable for sensing various species, people’s concern regarding the heavy metal content of II–VI QDs limit their wide-scale use, since the heavy-metal content might produce inevitable toxicity to human health and lead to environmental contamination [5,14]. As a result, the demand for developing novel kinds of fluorescent sensors made of heavy-metal-free fluorescent nanomaterials with good biocompatibility has been on the rise.

Sensors 2017, 17, 268; doi:10.3390/s17020268

www.mdpi.com/journal/sensors

2017, 16, 17, 2088 268 Sensors 2016,

2 of 15

On the other aspect, silicon, as the second-most abundant element in earth’s crust (28% by mass, the other as the second-most element in earth’s crust by with On oxygen being aspect, the mostsilicon, abundant) guarantees a richabundant and low-cost resource support for a(28% variety mass, with oxygen being the most abundant) guarantees a rich and low-cost resource support for of silicon-related applications, especially for the modern semiconductor industry [15]. Impressively, a variety of silicon-related applications, especiallyofforbulk the modern semiconductor industry [15]. distinguished from the poor photoluminescence silicon due to its indirect bandgap, Impressively, distinguished from the poor photoluminescence of bulk silicon due to its indirect nanometric-sized silicon shows distinct photoluminescence that benefits from the quantum bandgap, nanometric-sized shows distinct photoluminescence that benefits from the quantum confinement effect when thesilicon particle size is generally less than 5 nm [16,17]. In addition to the strong confinement effect when the particle size is generally less than 5 nm [16,17]. In addition to the fluorescence, the silicon nanomaterials usually feature photostability superior to that of common strong fluorescence, the silicon nanomaterials usually feature photostability superior to that of organic dyes and most semiconductor nanomaterials. For instance, upon high-power UV irradiation, common organictodyes most semiconductor instance, upon high-power in comparison rapidand fluorescence quenching nanomaterials. of fluorescein For isothiocyanate (FITC) (i.e., the UV irradiation, in comparison to rapid fluorescence quenching of fluorescein isothiocyanate (FITC) fluorescence quickly quenches after 5 min of UV irradiation) and relatively stable CdTe QDs or (i.e., the fluorescence quickly quenches after 5 min of UV irradiation) and relatively stable CdTe CdSe/ZnS QDs (i.e., the fluorescence can be retained for 120 min under UV irradiation), the prepared QDs or CdSe/ZnS QDs (i.e., thecan fluorescence can beand retained 120 min under irradiation), fluorescent silicon nanoparticles preserve strong stable for fluorescence under UV high-power UV the prepared fluorescent silicon nanoparticles can preserve strong and stable fluorescence under irradiation for 400 min [14]. More significantly, silicon nanomaterials (e.g., silicon nanoparticles high-power UVnanowires irradiation(SiNWs), for 400 min [14].nanorods More significantly, silicon (e.g., due silicon (SiNPs), silicon silicon (SiNRs), etc.) havenanomaterials little or no toxicity to nanoparticles (SiNPs), silicon nanowires (SiNWs), silicon nanorods (SiNRs), etc.) have little or no the benign biocompatibility of silicon, which is highly attractive for biomedical and biological toxicity due toRecent the benign biocompatibility of silicon, is highly attractive(e.g., for biomedical and applications. studies have demonstrated thatwhich silicon nanomaterials SiNPs, silicon biological applications. Recent studies haveand demonstrated that into silicon nanomaterials (e.g.,can SiNPs, nanoneedles) were easily biodegradable decomposed silicic acid, which be silicon nanoneedles) were easily biodegradable and decomposed into silicic acid, which can be subsequently cleared from the body via kidney without apparent toxicity [18,19]. The unique optical subsequently cleared from the body via kidney without apparent toxicity [18,19]. The unique properties combined with benign biocompatibility offer exciting opportunities for design of optical properties fluorescent combined with benign biocompatibility offer exciting opportunities for design high-performance sensors [20–22]. of high-performance fluorescent sensors [20–22]. Consequently, during the last decade, we have witnessed vast advancements in the Consequently, during the last decade, we have analytical witnessed platforms vast advancements in various the development development of silicon nanomaterial-based optical for sensing chemical of silicon nanomaterial-based optical analytical platforms for sensing various chemical and biological and biological species, including chemical reagents, metal ions, proteins, intracellular pH, and so species,To including chemical metal ions, proteins, pH, and forth. To date, there forth. date, there are reagents, some review-type articles intracellular mainly focusing onsothe introduction of are some review-type articlesquantum mainly focusing on the sensors, introduction of zero-dimensional siliconworks quantum zero-dimensional silicon dot-based omitting the significant of dot-based sensors, omitting the significant works of one-dimensional nanomaterial-based one-dimensional silicon nanomaterial-based fluorescent sensors [20–22].silicon Hence, in this review, we fluorescent sensors [20–22]. Hence, in this review, we will introduce the latest representative will introduce the latest representative achievements of zero/one-dimensional silicon achievements of zero/one-dimensional silicon nanomaterial-based fluorescent sensors in detail. nanomaterial-based fluorescent sensors in detail. As summarized in Figure 1, according to different As summarized in Figure 1, according to different dimensions of nanostructures, the silicon dimensions of nanostructures, the silicon nanomaterial-based fluorescent sensors mentioned in this nanomaterial-based fluorescent sensors mentioned in this review cover zeroone-dimensional review cover zero- and one-dimensional fluorescent silicon nanosensors. Weand further discuss the fluorescent silicon nanosensors. We further discuss the major challenges and prospects the major challenges and prospects for the development of silicon nanomaterial-based sensorsfor in the development of silicon nanomaterial-based sensors in the final section. final section.

Figure 1. Silicon nanomaterial-based fluorescent sensors constructed by using zero- and Figure 1. Silicon nanomaterial-based fluorescent sensors constructed by using zero- and one-dimensional silicon-based nanomaterials featuring several merits, and their use for various one-dimensional silicon-based nanomaterials featuring several merits, and their use for various sensing sensing applications. (Zero-dimensional silicon nanoparticles (SiNPs) image was reproduced with applications. (Zero-dimensional silicon nanoparticles (SiNPs) image was reproduced with permission permission ref. [23]. Copyright American Society. silicon One-dimensional silicon from ref. [23].from Copyright 2015, American2015, Chemical Society.Chemical One-dimensional nanowires (SiNWs) nanowires (SiNWs) image was reproduced with permission from [24]. Copyright 2014, John Wiley & image was reproduced with permission from [24]. Copyright 2014, John Wiley & Sons, Inc.) Sons, Inc.)

Sensors 2017, 17, 268

3 of 15

2. Preparation of Silicon Nanomaterials To date, numerous synthetic strategies have been proposed for the preparation of these silicon nanostructures. Since the topic of this review is not synthetic methods of silicon nanomaterials, we just briefly introduce recent representative strategies for preparation and functionalization of silicon-based nanomaterials. Readers who are interested in detailed fabrication protocols can refer to several excellent review published recently [14,20,25,26]. 2.1. Preparation of Zero-Dimensional Silicon Nanomaterials Fluorescence zero-dimensional SiNPs featuring unique optical properties (i.e., bright luminescence and a strong antiphotobleaching property) and feeble toxicity have extensively been exploited for fabricating new fluorescent nanosensors. So far, several synthetic approaches have been well developed for preparation of SiNPs, including laser pyrolysis [27], electrochemical and chemical etching [28,29], microemulsion [30,31], high-temperature processes [32], plasma-assisted synthesis [33,34], and so forth. Afterwards, in order to meet requirements of different applications, the as-prepared SiNPs need further surface modification, such as surface oxidation and etching [35], hydrosilylation [36], bioconjugation [23,37,38], and so forth. Some recent representative works concerning preparation and functionalization of SiNPs are as follows. In 2013, Nishimura et al. developed a novel chemical-etching method to prepare small-sized and photostable fluorescent SiNPs for single-molecule tracking and fluorescence imaging. In this case, the single-crystal silicon wafer was first immersed into HF–HNO3 solution to form the SiNPs terminated with hydroxyl groups (OH–SiNPs), which were further modified with mercaptotrimethoxysilane. Then, the functionalized SiNPs were detached from the silicon wafer by using a razor blade, followed by bioconjugation with maleimide derivatives [39]. In the same year, Atkins et al. utilized the metathesis reaction of silicon tetrachloride (SiCl4 ) with sodium silicide (Na4 Si4 ) and Zintl salts to obtain chloride-terminated SiNPs (Cl–SiNPs) with an average size of ~10 nm. Importantly, the surface of the as-prepared SiNPs can be further passivated with octylmagnesium bromide (C8 H17 MgBr), 4-aminophenylmagnesium bromide (C6 H6 NMgBr) via a Grignard reaction, respectively, providing both a nonpolar and polar surface group. In addition, the resultant Cl–SiNPs can also be passivated with aminopropyltrimethoxysilane (APTMS) to improve the crystallinity of the synthesized SiNPs [40]. In the following year, Veinot’s group reported that photoluminescence of SiNPs with a size of ~4 nm can be effectively tuned across the entire visible spectrum through surface group modification without changing the size of SiNPs. In their work, the oxide-embedded SiNPs were first prepared via disproportionation of hydrogen silsesquioxane (HSQ) at high temperature (e.g., 1100 ◦ C). Next, the oxide matrix of the resultant SiNPs could be removed by treatment with an acid HF solution, and the hydride-terminated SiNPs (H–SiNPs) were produced. The surface of H–SiNPs can be respectively modified with alkyl, amine, phosphine, or acetal functional groups, enabling regulation of emission of SiNPs [41]. In 2014, they further synthesized the hybrid particles combining poly (diethyl vinylphosphonate) (PDEVP) and fluorescent silicon nanocrystals in three steps. The as-resultant functionalized silicon nanocrystals displayed distinct thermoresponsive behavior, attributed to the temperature-dependent coiling of PDEVP, which led to the change of the nanohybrids’ hydrodynamic radius [42]. In the same year, they also prepared D-mannose- and L-alanine-functionalized water-soluble fluorescent silicon nanocrystals (SiNCs) and used them for MCF-7 cells imaging [43]. In order to further realize facile and large-scale synthesis of SiNPs, in 2015, Zhong et al. developed a one-pot strategy based on a photochemical approach for the preparation of water-dispersible and fluorescent SiNPs (~10 g in 40 min). They achieved a high photoluminescence quantum yield (PLQY) value of up to ~25% by employing 1, 8-naphthalimide to reduce the silicon source of (3-aminopropyl) trimethoxysilane under UV irradiation [23]. In the same year, as indicated in Figure 2A, the same group further introduced an environmentally friendly method for biomimetic preparation of fluorescent SiNPs with a narrow emission spectral width (e.g., full width at half-maximum (FWHM) of ~30 nm) in a rapid (10 min)

Sensors 2017, 17, 268

4 of 15

and environmentally Sensors 2016, 16, 2088 benign manner, by using diatoms as the green silicon precursor without 4 of 15extra chemical reagents [38]. The authors further employed these as-prepared water-dispersible SiNPs for water-dispersible SiNPs for long-term immunofluorescent cellular imaging via anti-mouse bioconjugation with long-term immunofluorescent cellular imaging via bioconjugation with goat IgG [23,39]. goat anti-mouse IgG [23,39]. More recently, Li et al. prepared nitrogen-capped silicon nanoparticles More recently, Li et al. prepared nitrogen-capped silicon nanoparticles with ultrahigh PLQY of up to with ultrahigh PLQY of up to 90% and narrow luminescence bandwidth (e.g., FWHM of ~40 nm) for 90% and narrow luminescence bandwidth (e.g., FWHM of ~40 nm) for which silicon tetrabromide which silicon tetrabromide (SiBr4), rather than SiCl4, is employed as precursor, as presented in (SiBr4Figure ), rather than SiCl4 , is employed as precursor, as presented in Figure 2B [44]. 2B [44].

Figure 2. (A) Schematic illustration of biomimetic synthesis of fluorescent SiNPs and their use for in

Figure 2. (A) Schematic illustration of biomimetic synthesis of fluorescent SiNPs and their use for vitro and in vivo dual-color imaging. Reproduced with permission from ref. [38]. Copyright 2015, in vitro and in vivo dual-color imaging. Reproduced with permission from ref. [38]. Copyright 2015, American Chemical Society; (B) schematic illustration of synthesis of yellow-emitting SiNPs with American Chemical Society; (B) narrow schematic illustration of (PL) synthesis of yellow-emitting SiNPs with ultrahigh quantum yield and photoluminescence bandwidth; (I) scheme of synthetic ultrahigh quantumprocedures; yield and (II) narrow photoluminescence (PL) bandwidth; (I) scheme of synthetic and modified photograph of SiNPs in glyme under ambient light; (III) TEM image of and modified procedures; photographelectron of SiNPs in glymepattern under of ambient (III) TEM image of SiNPs. SiNPs. Inset is the(II) selected-area diffraction SiNPs;light; IV) PL, photoluminescence (PLE), and electron absorbance (Abs) spectra of SiNPs. Reproduced with permission fromexcitation [44]. Inset excitation is the selected-area diffraction pattern of SiNPs; IV) PL, photoluminescence 2016, American Chemical Society. Reproduced with permission from [44]. Copyright 2016, (PLE),Copyright and absorbance (Abs) spectra of SiNPs. American Chemical Society. 2.2. Preparation of One-Dimensional Silicon Nanomaterials

Significantly different from zero-dimensional 2.2. Preparation of One-Dimensional Silicon Nanomaterials silicon nanomaterials, one-dimensional fluorescent silicon nanostructures could largely lower thresholds for optical gain and multiexciton

Significantly different from zero-dimensional silicon nanomaterials, one-dimensional fluorescent generation owing to radiative electron-hole recombination rates and Auger recombination [45]. silicon nanostructures could largely lower thresholds for optical gain and multiexciton generation Consequently, these unique optical properties existing in one-dimensional nanostructures are vital owing radiative electron-hole recombination andHowever, Auger recombination [45]. fortothe construction of high-performance opticalrates sensors. to date, there are fewConsequently, examples high-quality silicon nanostructures, which might be due to relatively these of unique opticalfluorescent propertiesone-dimensional existing in one-dimensional nanostructures are vital for the construction tedious synthetic procedures, extreme experimental conditions, and low quantum yield (QY) values. of high-performance optical sensors. However, to date, there are few examples of high-quality For instance, Korgel et al. presented the first demonstration of one-dimensional fluorescent silicon fluorescent one-dimensional silicon nanostructures, which might be due to relatively tedious synthetic nanorods (SiNRs) but with low QY values of ~4%–5% based on solution-liquid-solid growth and procedures, extreme experimental conditions, and low quantum yield (QY) values. For instance, HF-etching treatment process [46]. To address this issue, Song et al. prepared size-tunable Korgel et al. presented the first demonstration of one-dimensional fluorescent silicon nanorods (SiNRs) fluorescent SiNRs with the relatively high QY of ~15% and strong photostability (maintaining ~90% but with low QY values of ~4%–5% based on solution-liquid-solid growth and HF-etching treatment of the initial intensity under UV irradiation for 400 min) through one-pot microwave synthesis. As process [46].in To address issue, Songprocess et al. ofprepared size-tunable fluorescent SiNRsfusion with the shown Figure 3, the this whole synthetic SiNRs contains three typical steps: micelle relatively high QY of ~15% crystal and strong photostability (maintaining ~90% of therate initial intensity under and crystal nucleation, growth and aggregation, and different growth in longitudinal UV irradiation 400interestingly, min) throughthe one-pot microwave synthesis. As shown in Figureexcitation 3, the whole direction. for More as-prepared SiNRs show nearly continuous wavelength-dependent emission behavior, which can be employed as a promising fluorescent label synthetic process of SiNRs contains three typical steps: micelle fusion and crystal nucleation, crystal for multicolor imaging [47]. Despite these elegant works, the design and fabrication of growth and aggregation, and different growth rate in longitudinal direction. More interestingly, one-dimensional fluorescent silicon nanomaterial-based sensors is still rare. the as-prepared SiNRs show nearly continuous excitation wavelength-dependent emission behavior, On the other aspect, numerous signal-off fluorescent sensors are designed and fabricated that which can be employed as a promising fluorescent label for multicolor imaging [47]. Despite these take advantage of unique features of non-luminescent silicon nanowires (SiNWs), which show elegant works, the design and fabrication of one-dimensional fluorescent silicon nanomaterial-based strong high fluorescence quenching efficiency (>90%). Nowadays, the well-established fabrication sensors is still rare.

Sensors 2017, 17, 268

5 of 15

On the other aspect, numerous signal-off fluorescent sensors are designed and fabricated that take advantage of unique features of non-luminescent silicon nanowires (SiNWs), which show Sensors strong fluorescence quenching efficiency (>90%). Nowadays, the well-established 2016,high 16, 2088 5 of 15 fabrication techniques of SiNWs—such as chemical vapor deposition (CVD) [48], oxide-assisted techniques of SiNWs—such as chemical vaporetching deposition (CVD) [48], growth (OAG) the growth (OAG) [49], metal-catalyzed electroless [50,51], and sooxide-assisted on—significantly facilitate [49], metal-catalyzed electroless etching [50,51], and so on—significantly facilitate the preparation preparation of SiNW-based fluorescent sensors. In addition, SiNWs can be readily modifiedofwith SiNW-based fluorescent sensors. In addition, SiNWs can be readily modified with metallic metallic nanoparticles (e.g., AuNPs, AgNPs, iron oxide nanoparticles (IONPs), etc.) to produce SiNWs nanoparticles (e.g., AuNPs, AgNPs, iron oxide nanoparticles (IONPs), etc.) to produce SiNWs nanohybrids. Such processes are usually based on the galvanic displacement reactions, in which nanohybrids. Such processes are usually based on the galvanic displacement reactions, in which − ) can − + 4ethe the electrons from the surfaces of SiNWs generated by HF etching (Si + 6F− → SiF6 2effectively electrons from the surfaces of SiNWs generated by HF etching (Si + 6F− → SiF6 2− + 4e−) can effectively theions metal ions metallic to form nanoparticle-modified metallic nanoparticle-modified SiNWs [52,53]. reducereduce the metal to form SiNWs [52,53].

(A) Schematic illustration thewhole wholegrowth growth process (B–I) TEM andand HRTEM FigureFigure 3. (A)3.Schematic illustration ofofthe processofofSiNRs; SiNRs; (B–I) TEM HRTEM images of silicon nanorods (SiNRs) with different lengths: (B,F) 250 nm; (C,G) 180 nm; (D,H) nm; 140 images of silicon nanorods (SiNRs) with different lengths: (B,F) 250 nm; (C,G) 180 nm;140 (D,H) and (E,I) 100 nm at different milk concentrations ranging from 1 to 4 mg/mL. Insets in (B–E) nm; and (E,I) 100 nm at different milk concentrations ranging from 1 to 4 mg/mL. Insets in (B–E) represent corresponding length distribution analysis (histograms) determined by TEM and dynamic represent corresponding length distribution analysis (histograms) determined by TEM and dynamic laser light scattering (DLS) spectra (blue curves). Reproduced with permission from [47]. Copyright laser light scattering (DLS) spectra (blue curves). Reproduced with permission from [47]. Copyright 2016, American Chemical Society. 2016, American Chemical Society.

3. Applications of Silicon Nanomaterial-Based Fluorescent Sensors

3. Applications of Silicon Nanomaterial-Based Fluorescent Sensors 3.1. Zero-Dimensional Silicon Nanomaterial-Based Fluorescent Sensors

3.1. Zero-Dimensional Silicon Nanomaterial-Based Fluorescent Sensors Based on the elegant work of synthesis of zero-dimensional fluorescent SiNPs, scientists have furtheron devoted tremendous to developing various kinds offluorescent fluorescent SiNP-based sensorshave Based the elegant work efforts of synthesis of zero-dimensional SiNPs, scientists for monitoring chemical and biological species, including heavy metal ions, explosives, glucose, further devoted tremendous efforts to developing various kinds of fluorescent SiNP-based sensors for pesticides, antibiotics, dopamine, intracellular pH, and so forth [54–67]. monitoring chemical and biological species, including heavy metal ions, explosives, glucose, pesticides, As for the detection of heavy metal ions, in 2014, Yu et al. developed a selective and recyclable antibiotics, dopamine,2+intracellular pH, and so forth [54–67]. mercuric ion (Hg ) sensor based on highly fluorescent SiNPs (e.g., PLQY of ~21.6%), which was As for thethrough detection heavy metaltreatment ions, in 2014, Yu etinal.the developed a selective and recyclable prepared theof hydrothermal of APTMS presence of sodium citrate. Only 2+ ) sensor based on highly fluorescent SiNPs (e.g., PLQY of ~21.6%), which was mercuric ion (Hg Hg2+ can distinctly quench the fluorescence of SiNPs due to the strong interaction between biothiols 2+ prepared hydrothermal APTMS in theand presence of detection sodium citrate. and through Hg2+. Thethe SiNP-based sensor treatment can realize of rapid, label-free, sensitive of Hg2+ Only with aHg can distinctly the50 fluorescence of SiNPs due to theasstrong biothiols detection quench range from nM to 1 μM and a detection limit low asinteraction 50 nM. Morebetween importantly, it can and 2+ be regenerative for at least five cycles by the addition of ethylenediaminetetraacetic acid (EDTA) Hg . The SiNP-based sensor can realize rapid, label-free, and sensitive detection of Hg2+ with solutionrange [55]. In the same year, al. used silicon quantum as novel fluorescent a detection from 50 nM to Zhao 1 µMetand a detection limit asdots low(SiQDs) as 50 nM. More importantly, probes for the detection of copper ions (Cu2+) in a label-free, selective, and sensitive manner [56]. In

Sensors 2017, 17, 268

6 of 15

it can be regenerative for at least five cycles by the addition of ethylenediaminetetraacetic acid (EDTA) solution [55]. In the same year, Zhao et al. used silicon quantum dots (SiQDs) as novel 2+ fluorescent Sensors 2016,probes 16, 2088 for the detection of copper ions (Cu ) in a label-free, selective, and sensitive 6 of 15 manner [56]. In their study, the SiQDs were prepared through the classical electrochemical etching their study, the SiQDs were prepared through electrochemical method.radicals The method. The fluorescence of as-prepared SiQDsthe canclassical be effectively quenchedetching by hydroxyl 2+ fluorescence of as-prepared SiQDs can be effectively quenched by hydroxyl radicals produced by produced by the Fenton reaction between Cu and H2 O2 (Figure 4A). The fluorescence is linearly 2+ and H2O2 (Figure 4A). The fluorescence is linearly quenched as a 2+ the Fenton reaction between Cu quenched as a function of Cu concentration ranging from 25 to 600 nM. The limit of detection was as function of much Cu2+ concentration ranging from 25 to 600 nM. The limit of detection as low as 8 nM, low as 8 nM, lower than those of existing approaches [56]. More recently,was in 2016, King-Chuen much lower than those of existing approaches [56]. More recently, in 2016, King-Chuen Lin’s group 2+ 2+ 2+ Lin’s group detected individual Mg , Ca , and Mn metal ions in live cells based on turn-on detected individual Mg2+, Ca2+, and Mn2+ metal ions in live cells based on turn-on fluorescent SiQDs fluorescent SiQDs sensors in selective and sensitive manners (e.g., the detection limit of Mg2+ , Ca2+ , 2+, Ca2+, and Mn2+ is 1.81, sensors in selective and sensitive manners (e.g., the detection limit of Mg and Mn2+ is 1.81, 3.15, and 0.47 µM, respectively). In their study, when SiQDs were coordinated with 3.15, and 0.47 μM, respectively). In their study, when SiQDs were coordinated with aza-crown aza-crown ethers, the fluorescence of SiQDs was diminished, ascribed to photoinduced electron transfer ethers, the fluorescence of SiQDs was diminished, ascribed to photoinduced electron transfer (PET) (PET) from the aza-crown ethers’ moiety to the valence band of SiQDs. Remarkably, the fluorescence from the aza-crown ethers’ moiety to the valence band of SiQDs. Remarkably, the fluorescence can canbeberecovered recoveredininthe thepresence presenceofofmetal metalions ionsowing owingtotothe thestrong strongcharge-electron charge-electron binding force binding force between the metal ions and aza-crown ether (Figure 4B) [57]. between the metal ions and aza-crown ether (Figure 4B) [57].

2+ based on label-free silicon quantum Figure (A) Illustrationofofthe thestrategy strategyfor forthe thedetection detection of of Cu Cu2+ Figure 4. 4. (A) Illustration based on label-free silicon quantum dots (SiQDs) and Fenton reaction. Reproduced with permission 2014, Elsevier. dots (SiQDs) and Fenton reaction. Reproduced with permissionfrom from[56]. [56].Copyright Copyright 2014, Elsevier. (B) Schematic representation for the PET process and subsequent suppression of photoinduced (B) Schematic representation for the PET process and subsequent suppression of photoinduced electron electron transfer (PET) between the aza-crown ethers’ moiety and SiQDs in the absence and transfer (PET) between the aza-crown ethers’ moiety and SiQDs in the absence and presence of metal presence of metal ions. Reproduced with permission from [57]. Copyright 2016, American Chemical ions. Reproduced with permission from [57]. Copyright 2016, American Chemical Society. Society.

AsAsforforexplosives, paper-basedsensors sensorsmade madeof of explosives, Veinot’s Veinot’s group group developed developed disposable, disposable, paper-based dodecyl-functionalized containingnitroaromatic, nitroaromatic, nitroamine, dodecyl-functionalizedSiNPs SiNPsfor forthe the detection detection of explosives explosives containing nitroamine, and nitrate ester atatnanogram paper-basedsensors sensorsare arefabricated fabricated through and nitrate ester nanogramlevels levels[58]. [58]. Typically, such paper-based through dip-coating filter paper in a toluene solution containing SiNPs. In the presence of mononitrotoluene (MNT), dinitrotoluene (DNT), trinitrotoluene (TNT), cyclotrimethylenetrinitramine (RDX), and pentaerythritol tetranitrate (PETN), the fluorescence of paper-based sensors was rapidly quenched.

Sensors 2017, 17, 268

7 of 15

dip-coating filter paper in a toluene solution containing SiNPs. In the presence of mononitrotoluene (MNT), dinitrotoluene (DNT), trinitrotoluene (TNT), cyclotrimethylenetrinitramine (RDX), and pentaerythritol tetranitrate (PETN), the fluorescence of paper-based sensors was rapidly quenched. In addition, the sensors showed obvious quenching effects when exposed to solid or vapor residue of nitroaromatic compounds. The quenching results are supposed to stem from electron transfer from SiNPs to the π-orbitals of the nitro compounds. Interestingly, the quenching phenomena were reversible when exposed to volatile compounds [59]. In 2015, Ban et al. developed water-dispersible amino-capped SiNPs as fluorescent sensors for the detection of TNT in aqueous medium [59]. The authors claimed that TNT formed a complex with the surface amino groups of SiNPs through Sensors 2016, 16, 2088 7 of 15 strong donor/acceptor interactions. The resultant TNT/amine complex strongly quenched the In addition, the sensors showedresonance obvious quenching when(FRET) exposed to solid or vapor fluorescence of SiNPs via Forster energyeffects transfer process. The residue authors further of nitroaromatic compounds. The quenching results are supposed to stem from electron transfer demonstrated that the quenching efficiencies depended on the binding affinities of nitro analytes on from SiNPs to the π-orbitals of the nitro compounds. Interestingly, the quenching phenomena were the SiNPs’reversible surface when and the electron-accepting ability nitro compounds In 2016, Prof. Sohn’s exposed to volatile compounds [59].ofInthe 2015, Ban et al. developed[59]. water-dispersible group utilized blue-emitting forsensors the detection of 2,3-dimethyl-2,3-dinitrobutane (DMNB). In amino-capped SiNPs as SiQDs fluorescent for the detection of TNT in aqueous medium [59]. The that TNT formed a complex with the surface amino groupssilicide of SiNPs with through strong this case, authors SiQDsclaimed were obtained through the reaction of magnesium ethylenediamine donor/acceptor interactions. The resultant TNT/amine complex strongly quenched the fluorescence dihydrochloride. The as-prepared SiQDs showed better sensitivity in the detection of DMNB compared of SiNPs via Forster resonance energy transfer (FRET) process. The authors further demonstrated to CdSe QDs to their higher lying conduction [60]. In theofsame year, Jonathan G. C. Veinot’s that due the quenching efficiencies depended on the band binding affinities nitro analytes on the SiNPs’ group used silicon quantum dot sensors—terminating with three of surface groups (alkyl surface and the electron-accepting ability of the nitro compounds [59]. Inkinds 2016, Prof. Sohn’s group blue-emitting SiQDs foramine)—to the detection detect of 2,3-dimethyl-2,3-dinitrobutane (DMNB). In this(e.g., solid, oligomer, utilized alkyl monomer, and alkyl nitroaromatics in different phases case, SiQDs were obtained through the reaction of magnesium silicide with ethylenediamine liquid, and vapor phases). In this study, the sensors were made of simple and inexpensive filter dihydrochloride. The as-prepared SiQDs showed better sensitivity in the detection of DMNB papers, dipped into silicon solution, on which of Jonathan silicon quantum compared to CdSe QDsquantum due to theirdots higher lying conduction bandthe [60].fluorescence In the same year, dots is quenched in thegroup presence of nitroaromatics due to the electron transfer quenching mechanism G. C. Veinot’s used silicon quantum dot sensors—terminating with three kinds of surface groups (Figure 5A) [61]. (alkyl oligomer, alkyl monomer, and alkyl amine)—to detect nitroaromatics in different phases (e.g., solid, liquid, and vapor phases). In this study, the sensors were made of simple and For other organic compounds, in 2015, Zhang et al. developed an ultrasensitive dopamine inexpensive filter papers, dipped into silicon quantum dots solution, on which the fluorescence of (DA) detection withis the lowest (~0.3 nM) assisted bydue water-soluble silicon method quantum dots quenched in limit the presence of nitroaromatics to the electron SiNPs transfer with high quenching mechanism (Figure 5A)prepared [61]. quantum yield of ~23.6%, which were by using a one-pot synthetic method under microwave other organic compounds, effect in 2015,on Zhang et al.induced developedonly an ultrasensitive (DA) irradiation. InFor particular, a quenching SiNPs by the DAdopamine molecule (rather than detection method with the lowest limit (~0.3 nM) assisted by water-soluble SiNPs with high other molecules) was observed, owing to the energy transfer between SiNPs and oxidized dopamine quantum yield of ~23.6%, which were prepared by using a one-pot synthetic method under moleculesmicrowave through irradiation. FRET effect. Moreover, thereeffect wasonaSiNPs linear relationship fluorescence In particular, a quenching induced only by thebetween DA molecule (rather than molecules) was observed, the to energy between intensity change andother DA concentrations rangingowing from to 0.005 10.0transfer µM (Figure 5B)SiNPs [62].and In 2016, Jose oxidizeda dopamine through FRET effect. there was a linear silicon relationship et al. developed signal-offmolecules fluorescent sensor made ofMoreover, hexadecylamine-capped nanoparticles between fluorescence intensity change and DA concentrations ranging from 0.005 to 10.0 μM (Figure (SiNPs) for the determination of Sudan dyes I, which were extensively adulterating food products. 5B) [62]. In 2016, Jose et al. developed a signal-off fluorescent sensor made of −5 to 4.97 × 10−7 M, with a detection limit Sudan I can be quantified within the range of (SiNPs) 2.91 ×for 10the hexadecylamine-capped silicon nanoparticles determination of Sudan dyes I, which −8 extensively were foodetproducts. Sudan I dual-mode can be quantified within the range 2.91 × of 3.90 × 10 M [63]. Inadulterating 2016, Wang al. presented amperometric andofoptical-sensing −5 to 4.97 × 10−7 M, with a detection limit of 3.90 × 10−8 M [63]. In 2016, Wang et al. presented 10 strategy for the detection of glucose by using a fluorescent SiNP-coated electrode, which is more dual-mode amperometric and optical-sensing strategy for the detection of glucose by using a sensitive than a glucose oxidase electrode [64]. fluorescent SiNP-coated electrode, which is more sensitive than a glucose oxidase electrode [64].

Figure 5. Cont.

Sensors 2017, 17, 268 Sensors 2016, 16, 2088

8 of 15 8 of 15

Figure 5. (A) Illustration of the strategy for the preparation of alkyl monomer—(top), alkyl

Figure 5. (A) Illustration of the strategy for the preparation of alkyl monomer—(top), alkyl oligomer—(middle), and alkyl amine—(bottom) capped SiQDs. Inset represents photographs of a oligomer—(middle), and alkyl amine—(bottom) capped SiQDs. Inset represents photographs of quantum-dot filter paper, excited using a black light and with a 550 nm long-pass filter held in front a quantum-dot filter paper, excited using a black with aa thumb 550 nmimprint long-pass filterregion. held in front of the camera. (A) Pristine paper; (B) the samelight paperand showing as a dark Reproduced permission ref.same [61]. paper Copyright 2016, a IOPscience. (B): (I) as Schematic of the camera. (A) with Pristine paper; from (B) the showing thumb imprint a dark region. illustration SiNP-basedfrom sensor for[61]. the detection of dopamine (DA); (II) selectivity of as-prepared Reproduced with of permission ref. Copyright 2016, IOPscience. (B): (I) Schematic illustration SiNP-based sensor. with [62]. 2015, Chemical of SiNP-based sensor for Reproduced the detection of permission dopaminefrom (DA); (II)Copyright selectivity of American as-prepared SiNP-based Society. sensor. Reproduced with permission from [62]. Copyright 2015, American Chemical Society. Besides, for the detection of species in vitro, silicon nanomaterial-based fluorescent sensors can also befor used fordetection intracellular in vivo For instance, in 2016, Chu et al. fluorescent presented thesensors first Besides, the ofand species inanalysis. vitro, silicon nanomaterial-based can demonstration of fluorescent SiNP-based sensors for real-time and long-time intracellular pH (pH i) also be used for intracellular and in vivo analysis. For instance, in 2016, Chu et al. presented the measurement in live cells. As revealed in Figure 6, the resultant pH sensors were made of first demonstration of fluorescent SiNP-based sensors for real-time and long-time intracellular pH functionalized silicon nanoparticles, which were modified with both pH-sensitive dopamine (pHi ) measurement live cells. As revealed in Figure 6, (RBITC) the resultant pH[67]. sensors werethemade of molecules and in pH-insensitive rhodamine B isothiocyanate molecules Typically, functionalized silicon nanoparticles, which were modified with both pH-sensitive dopamine as-prepared sensors feature a wide-pH range response (~4–10), strong fluorescence (high PLQYmolecules of ~15%–25%), excellent photostability (~9% loss of (RBITC) intensity after 40 min of continual UV irradiation), and pH-insensitive rhodamine B isothiocyanate molecules [67]. Typically, the as-prepared feeblea cytotoxicity (cell viability of treated cells remains above 95% during 24 h treatment). sensors and feature wide-pH range response (~4–10), strong fluorescence (high PLQY of ~15%–25%), Taking advantage of these outstanding features, the developed sensors are especially suitable for the excellent photostability (~9% loss of intensity after 40 min of continual UV irradiation), and feeble ratiometric measurement of dynamic pH fluctuations and pHi changes in long-term and real-time cytotoxicity (cell viability of treated cells remains above 95% during 24 h treatment). Taking advantage manners [67]. of these outstanding features, the developed sensors are especially suitable for the ratiometric measurement of dynamic pH fluctuations and pHi changes in long-term and real-time manners [67].

Sensors 2017, 17, 268 Sensors 2016, 16, 2088

9 of 15 9 of 15

Figure 6. Construction of SiNP-based intracellular pH sensor. (A) Schematic illustration of the Figure 6. Construction of SiNP-based intracellular pH sensor. (A) Schematic illustration of the synthesis of sensor; (B) photos of SiNPs (1), dopamine (2), rhodamine B isothiocyanate (RBITC) (3), synthesis of sensor; (B) photos of SiNPs (1), dopamine (2), rhodamine B isothiocyanate (RBITC) (3), and modified SiNPs (4) in ambient environment and under UV irradiation (λex = 360 nm) as well as and modified SiNPs (4) in ambient environment and under UV irradiation (λex = 360 nm) as well as TEM image of dual-modified SiNPs (DMSiNPs). Inset shows the enlarged HRTEM image of a single TEM DMSiNP; image of (C) dual-modified SiNPs (DMSiNPs). Inset shows of theDMSiNPs. enlargedInset HRTEM image of a single schematic illustration of cellular internalization in part C presents DMSiNP; (C) schematic illustration of cellular internalization of DMSiNPs. Inset in part C presents charge-transfer mechanism of DMSiNPs at acidic or basic conditions. Reproduced with permission charge-transfer mechanism DMSiNPs at acidic or basic conditions. Reproduced with permission from [67]. Copyright 2016,of American Chemical Society. from [67]. Copyright 2016, American Chemical Society. 3.2. One-Dimensional Silicon Nanomaterial-Based Fluorescent Sensors

3.2. One-Dimensional Silicon Nanomaterial-Based Fluorescent Sensors SiNWs feature strong fluorescence quenching efficiency (>90%). Based on this advantage of SiNWs, they have been designed and fabricated as several high-performance fluorescent sensors, in

SiNWs feature strong fluorescence quenching efficiency (>90%). Based on this advantage of which SiNWs usually acted as a quencher. For instance, as far back as 2008, Lee and co-workers SiNWs, they have been designed and fabricated as several high-performance fluorescent2+ sensors, constructed a kind of SiNW-based fluorescent sensor for the detection of free copper ions (Cu ) in in which SiNWs as a[68]. quencher. as were far back as 2008, Lee andwith co-workers sensitive andusually selectiveacted manners In this For case,instance, the SiNWs covalently modified the constructed a kind of SiNW-based fluorescent sensor for the detection of free copper ions (Cu2+ ) fluorescence ligand of N-(quinoline-8-yl)-2-(3-triethoxysilyl-propylamino)-acetamide (QIOEt). in sensitive and In this case, the SiNWs were covalently modified Based on the selective observed manners changes of[68]. fluorescence intensities of QIOEt, low-concentration (10−8 M) with free the 2+ fluorescence ligand of N-(quinoline-8-yl)-2-(3-triethoxysilyl-propylamino)-acetamide (QIOEt). Cu could be readily discriminated. Distinguishing from such SiNW-based sensors for the detectionBased −8 M) of observed free Cu2+, changes in 2014, Shi’s group developed a newof SiNW-based fluorescent sensor,(10 which can be Cu2+ on the of fluorescence intensities QIOEt, low-concentration free 2+ for sensing both free andDistinguishing complexed Cu from in liver extract, and thosesensors releasedfor from couldused be readily discriminated. such SiNW-based theapoptotic detection of HeLa cells [69]. As shown in Figure 7, SiNWs prepared via the conventional thermal evaporation 2+ free Cu , in 2014, Shi’s group developed a new SiNW-based fluorescent sensor, which can be used method were covalently conjugated with 3-[2-(2-aminoethylamino)-ethylamino] for sensing both free and complexed Cu2+ in liver extract, and those released from apoptotic HeLa propyl-trimethoxysilane (3-A) and ansyl group, in which 3-A can selectively recognize Cu2+ over cells [69]. As shown in Figure 7, SiNWs prepared via the conventional thermal evaporation method other metal ions and numerous biomolecules. In addition, the developed sensor can effectively were detect covalently with 3-[2-(2-aminoethylamino)-ethylamino] 2+ with low detection free Cuconjugated limits as low as ~31 nM and a good dynamicpropyl-trimethoxysilane range from 50 to 400 (3-A)nM. andMore ansylimportantly, group, in which 3-A can selectively Cu2+ other as metal ions and Cu-Zn-superoxide dismutase recognize (SOD1) from realover samples, a typical numerous biomolecules. In can addition, the developed sensor can detect freesensor, Cu2+ with copper-binding enzyme, be quantitatively discriminated by effectively the developed SiNW indicatinglimits this sensor featured detect the complexed Cu2+ [69]. low detection as low as ~31the nMability and atogood dynamic range from 50 to 400 nM. More importantly, Cu-Zn-superoxide dismutase (SOD1) from real samples, as a typical copper-binding enzyme, can be quantitatively discriminated by the developed SiNW sensor, indicating this sensor featured the ability to detect the complexed Cu2+ [69].

Sensors 2017, 17, 268

10 of 15

Sensors 2016, 16, 2088

10 of 15

Figure 7. SiNW-based fluorescentsensors sensorsfor for the the detection detection of CuCu. 2+ (A): (I) Schematic Figure 7. SiNW-based fluorescent ofcomplexed complexed . (A): (I) Schematic illustration of procedures of the functionalization of SiNWs; (II) schematic illustration of illustration of procedures of the functionalization of SiNWs; (II) schematic illustration of SiNW-based 2+ based on fluorescence quenching; (B) SiNW-based sensors for the detection of complexed Cu sensors for the detection of complexed Cu2+ based on fluorescence quenching; (B) fluorescence fluorescence spectra of SiNWs-based sensors with addition of Cu-Zn-superoxide dismutase (SOD1) spectra of SiNWs-based sensors with addition of Cu-Zn-superoxide dismutase (SOD1) unit (I) and its unit (I) and its corresponding titration curve (II); λex = 350 nm, λem = 505 nm. Reproduced with corresponding titration curve (II); λex = 350 nm, λem = 505 nm. Reproduced with permission from [69]. permission from [69]. Copyright 2014, American Chemical Society. Copyright 2014, American Chemical Society. 2+

Besides the detection of heavy metallic ions, SiNW-based fluorescent sensors can also be workablethe fordetection discriminating DNA. In 2012, LeeSiNW-based and coworkers utilized SiNWs as can the also fluorescence Besides of heavy metallic ions, fluorescent sensors be workable quencher to build a multicolor molecular beacons (MBs) sensor, which was made of for discriminating DNA. In 2012, Lee and coworkers utilized SiNWs as the fluorescence quencher AuNP-decorated SiNWs (AuNPs@SiNWs) [70]. In such a case, target DNA was readily detected via to build a multicolor molecular beacons (MBs) sensor, which was made of AuNP-decorated SiNWs the AuNPs@SiNW-based MBs sensor by measuring the alteration of fluorescence intensity caused by (AuNPs@SiNWs) [70]. In such a case, target DNA was readily detected via the AuNPs@SiNW-based the conformation change of MBs due to the DNA hybridization. Of particular significance, MBs sensor by measuring the alteration of fluorescence intensity caused by the conformation change of compared to free AuNPs with relatively poor salt stability (e.g., obvious aggregation of AuNPs MBs due to the DNA hybridization. Of particular significance, compared to free AuNPs with relatively would be triggered by high-concentration salt solution), the resultant AuNPs@SiNW-based poor fluorescent salt stability (e.g.,featured obvious aggregation of M) AuNPs would be triggered by °C) high-concentration sensors high salt (e.g., ~0.1 and high temperature (e.g., ~80 tolerance. In salt solution), AuNPs@SiNW-based sensors featured high salttargets (e.g., ~0.1 addition, the resultant AuNPs@SiNW-based MBs could fluorescent simultaneously detect multiple DNA at M) approximately picomolar since various DNA strands were able to assemble on theMBs hugecould and high temperature (e.g., levels ~80 ◦ C) tolerance. In addition, the AuNPs@SiNW-based surface of the AuNPs@SiNWs [70]. targets More recently, Xie et al. further developed type ofDNA simultaneously detect multiple DNA at approximately picomolar levels another since various SiNW-based fluorescent sensor based on a new assembly strategy without introduction of AuNPs strands were able to assemble on the huge surface of the AuNPs@SiNWs [70]. More recently, Xie et al. [24], as shown in Figure 8. DNA strands were directly modified on the surface of the SiNWs based further developed another type of SiNW-based fluorescent sensor based on a new assembly strategy on the covalent conjugation with glutaraldehyde (GA), which could be further conjugated with without introduction of AuNPs [24], as shown in Figure 8. DNA strands were directly modified on the stem-loop DNA strands. Consequently, such a sensor enables high-efficacy detection of target DNA surface ofathe SiNWs basedason the conjugation with glutaraldehyde (GA), which could be with limit of detection low ascovalent ~1 pM [24]. further conjugated with stem-loop DNA strands. Consequently, such a sensor enables high-efficacy detection of target DNA with a limit of detection as low as ~1 pM [24].

Sensors 2017, 17, 268 Sensors 2016, 16, 2088

11 of 15 11 of 15

Figure 8. Schematic (A) Schematic diagram construction of of SiNW-based SiNW-based fluorescent sensor forfor DNA and and Hg Hg2+ Figure 8. (A) diagram ofofconstruction fluorescent sensor DNA detection. (B): (I) Fluorescence spectra and (II) corresponding PL intensities of complementary target detection. (B): (I) Fluorescence spectra and (II) corresponding PL intensities of complementary target DNA with serial concentrations. (C): (I) Fluorescence spectra and (II) corresponding calibration DNA with serial concentrations. (C): (I) Fluorescence2+spectra and (II) corresponding calibration curve curve of SiNW-based sensors for detection of Hg with serial concentrations. Reproduced with of SiNW-based sensors for detection of Hg2+ with serial concentrations. Reproduced with permission permission from [24]. Copyright 2014, RSC. from [24]. Copyright 2014, RSC. 2+

4. Conclusions and Future Perspectives

4. Conclusions and Future Perspectives In this review, we have summarized the representative works to highlight the recent success in fabrication of different silicon nanomaterial-based sensors for various In this review, we havedimensional summarized the representative worksfluorescent to highlight the recent success in chemical and biological sensing applications. Thus far, great strides have been made in designing fabrication of different dimensional silicon nanomaterial-based fluorescent sensors for various chemical silicon nanomaterial-based fluorescent sensors in two different dimensions: zero-dimensional and biological sensing applications. Thus far, great strides have been made in designing silicon SiNP-based sensors and one-dimensional SiNW-based sensors. In particular, SiNPs with strong nanomaterial-based fluorescent sensors in two different dimensions: zero-dimensional SiNP-based luminescence and robust photostability have been developed as numerous kinds of fluorescent sensors and one-dimensional sensors. particular, SiNPs with strong luminescence sensors for the detection ofSiNW-based a myriad of species. OnInthe other hand, SiNWs/SiNW nanohybrids have and robust photostability have developed as numerous kinds offluorescent fluorescent sensors for the detection also been designed andbeen fabricated as several high-performance sensors by utilization of of a myriad of species. On the other hand, SiNWs/SiNW nanohybrids have also been designed high fluorescence quenching efficiency of SiNWs. While as silicon nanomaterial-based fluorescent sensors have shown great promise forfluorescence myriad and fabricated several high-performance fluorescent sensors by utilization of high biological and biomedical applications, there are still many major challenges or issues in this field. quenching efficiency of SiNWs. First, most sensing applications are limited in laboratorial environment, thus,great much promise effort is required While silicon nanomaterial-based fluorescent sensors have shown for myriad to demonstrate consolidated feasibility of the silicon nanomaterial-based fluorescent sensors for field. biological and biomedical applications, there are still many major challenges or issues in this practical analysis in real sample systems. Second, while various silicon nanomaterial-based First, most sensing applications are limited in laboratorial environment, thus, much effort is required fluorescent sensors are available for high-sensitivity and high-specificity bioassays, convincing and to demonstrate consolidated feasibility of the silicon nanomaterial-based fluorescent sensors for rational analytical mechanisms are still required. Third, there are few reports concerning in vitro and practical analysis in real sample systems. Second, while various silicon nanomaterial-based in vivo analysis based on silicon nanomaterials-based fluorescent sensors, severely limitingfluorescent their sensors are available for high-sensitivity and high-specificity bioassays, convincing and rational wide-ranging applications. Finally, further improvement of the stability and reliability of silicon analytical mechanisms are still required. there few reports vitro and for in vivo nanomaterial-based fluorescent sensors Third, is still in greatare demand, which concerning is of essentialin importance realbased applications. with the growing understanding of the challenges, silicon analysis on silicon Along nanomaterials-based fluorescent sensors, severely limiting their wide-ranging nanomaterial-based fluorescent sensors would newand avenues for myriad sensing studies, and applications. Finally, further improvement of the open stability reliability of silicon nanomaterial-based also hold high promise for widespread practical analytical applications. fluorescent sensors is still in great demand, which is of essential importance for real applications. Along with the growing understanding of the challenges, silicon nanomaterial-based fluorescent sensors Acknowledgments: This work was supported by National Basic Research Program of China (973 Program would open new avenues for myriad sensing studies, and also hold high promise for widespread Grants 2013CB934400 and 2012CB932400), NSFC (Grants 61361160412, 51072126, 21575096 and 21605109), and a practical analytical applications. Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), and China Postdoctoral Science Foundation (Grants 7131701914), as well as Collaborative Innovation

Acknowledgments: work wasand supported by National Basic Research Program of China (973 Program Grants Center of SuzhouThis Nano Science Technology (NANO−CIC). 2013CB934400 and 2012CB932400), NSFC (Grants 61361160412, 51072126, 21575096 and 21605109), and a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), and China Postdoctoral Science Foundation (Grants 7131701914), as well as Collaborative Innovation Center of Suzhou Nano Science and Technology (NANO−CIC).

Sensors 2017, 17, 268

12 of 15

Author Contributions: H.Y.W. and Y.H. wrote the manuscript. Conflicts of Interest: The authors declare no conflict of interest.

References 1.

2. 3.

4.

5. 6.

7.

8. 9.

10. 11. 12. 13. 14. 15. 16. 17. 18. 19.

20. 21.

Chinen, A.B.; Guan, C.M.; Ferrer, J.R.; Barnaby, S.N.; Merkel, T.J.; Mirkin, C.A. Nanoparticle probes for the detection of cancer biomarkers, cells, and tissues by fluorescence. Chem. Rev. 2015, 115, 10530–10574. [CrossRef] [PubMed] Lane, L.A.; Qian, X.; Nie, S. SERS nanoparticles in medicine: From label-free detection to spectroscopic tagging. Chem. Rev. 2015, 115, 10489–10529. [CrossRef] [PubMed] Iverson, N.M.; Barone, P.W.; Shandell, M.; Trudel, L.J.; Sen, S.; Sen, F.; Ivanov, V.; Atolia, E.; Farias, E.; McNicholas, T.P. In vivo biosensing via tissue-localizable near-infrared-fluorescent single-walled carbon nanotubes. Nat. Nanotechnol. 2013, 8, 873–880. [CrossRef] [PubMed] Kelley, S.O.; Mirkin, C.A.; Walt, D.R.; Ismagilov, R.F.; Toner, M.; Sargent, E.H. Advancing the speed, sensitivity and accuracy of biomolecular detection using multi-length-scale engineering. Nat. Nanotechnol. 2014, 9, 969–980. [CrossRef] [PubMed] Howes, P.D.; Chandrawati, R.; Stevens, M.M. Colloidal nanoparticles as advanced biological sensors. Science 2014, 346, 1247390. [CrossRef] [PubMed] Kim, H.N.; Lee, M.H.; Kim, H.J.; Kim, J.S.; Yoon, J. A new trend in rhodamine-based chemosensors: Application of spirolactam ring-opening to sensing ions. Chem. Soc. Rev. 2008, 37, 1465–1472. [CrossRef] [PubMed] Zhu, L.; Yuan, Z.; Simmons, J.T.; Sreenath, K. Zn(II)-coordination modulated ligand photophysical processes—The development of fluorescent indicators for imaging biological Zn(II) ions. RSC Adv. 2014, 4, 20398–20440. [CrossRef] [PubMed] Nolan, E.M.; Lippard, S.J. Small-molecule fluorescent sensors for investigating zinc metalloneurochemistry. Acc. Chem. Res. 2009, 42, 193–203. [CrossRef] [PubMed] Zhu, L.; Younes, A.H.; Yuan, Z.; Clark, R.J. 5-Arylvinylene-2,20 -bipyridyls: Bright “push–pull” dyes as components in fluorescent indicators for zinc ions. J. Photochem. Photobiol. A 2015, 311, 1–15. [CrossRef] [PubMed] Chen, Y.; Bai, Y.; Han, Z.; He, W.; Guo, Z. Photoluminescence imaging of Zn2+ in living systems. Chem. Soc. Rev. 2015, 44, 4517–4546. [CrossRef] [PubMed] Silvi, S.; Credi, A. Luminescent sensors based on quantum dot-molecule conjugates. Chem. Soc. Rev. 2015, 44, 4275–4289. [CrossRef] [PubMed] Dennis, A.M.; Rhee, W.J.; Sotto, D.; Dublin, S.N.; Bao, G. Quantum dot-fluorescent protein FRET probes for sensing intracellular pH. ACS Nano 2012, 6, 2917–2924. [CrossRef] [PubMed] Orte, A.; Alvarez-Pez, J.M.; Ruedas-Rama, M.J. Fluorescence lifetime imaging microscopy for the detection of intracellular pH with quantum dot nanosensors. ACS Nano 2013, 7, 6387–6395. [CrossRef] [PubMed] Peng, F.; Su, Y.; Zhong, Y.; Fan, C.; Lee, S.T.; He, Y. Silicon nanomaterials platform for bioimaging, biosensing, and cancer therapy. Acc. Chem. Res. 2014, 47, 612–623. [CrossRef] [PubMed] He, Y.; Su, Y.Y. Silicon Nano-Biotechnology; Springer: Heidelberg, Germany, 2014. Tilley, R.D.; Yamamoto, K. The microemulsion synthesis of hydrophobic and hydrophilic silicon nanocrystals. Adv. Mater. 2006, 18, 2053–2056. [CrossRef] Takagahara, T.; Takeda, K. Theory of the quantum confinement effect on excitons in quantum dots of indirect-gap materials. Phys. Rev. B 1992, 46, 15578. [CrossRef] Park, J.H.; Gu, L.; Von Maltzahn, G.; Ruoslahti, E.; Bhatia, S.N.; Sailor, M.J. Biodegradable luminescent porous silicon nanoparticles for in vivo applications. Nat. Mater. 2009, 8, 331–336. [CrossRef] [PubMed] Chiappini, C.; De Rosa, E.; Martinez, J.; Liu, X.; Steele, J.; Stevens, M.; Tasciotti, E. Biodegradable silicon nanoneedles delivering nucleic acids intracellularly induce localized in vivo neovascularization. Nat. Mater. 2015, 14, 532–539. [CrossRef] [PubMed] Dasog, M.; Kehrle, J.; Rieger, B.; Veinot, J.G. Silicon nanocrystals and silicon-polymer hybrids: Synthesis, surface engineering, and applications. Angew. Chem. Int. Ed. 2016, 7, 2322–2339. [CrossRef] [PubMed] Su, Y.; Ji, X.; He, Y. Water-dispersible fluorescent silicon nanoparticles and their optical applications. Adv. Mater. 2016. [CrossRef] [PubMed]

Sensors 2017, 17, 268

22. 23.

24.

25.

26. 27. 28.

29.

30. 31. 32.

33. 34. 35.

36.

37.

38.

39.

40.

41.

13 of 15

Gonzalez, C.M.; Veinot, J.G.C. Silicon nanocrystals for the development of sensing platforms. J. Mater. Chem. C 2016, 4, 4836–4846. [CrossRef] Zhong, Y.; Sun, X.; Wang, S.; Peng, F.; Bao, F.; Su, Y.; Li, Y.; Lee, S.T.; He, Y. Facile, large-quantity synthesis of stable, tunable-color silicon nanoparticles and their application for long-term cellular imaging. ACS Nano 2015, 9, 5958–5967. [CrossRef] [PubMed] Xie, J.; Jiang, X.; Zhong, Y.; Lu, Y.; Wang, S.; Wei, X.; Su, Y.; He, Y. Stem-loop DNA-assisted silicon nanowires-based biochemical sensors with ultra-high sensitivity, specificity, and multiplexing capability. Nanoscale 2014, 6, 9215–9222. [CrossRef] [PubMed] Montalti, M.; Cantelli, A.; Battistelli, G. Nanodiamonds and silicon quantum dots: Ultrastable and biocompatible luminescent nanoprobes for long-term bioimaging. Chem. Soc. Rev. 2015, 44, 4853–4921. [CrossRef] [PubMed] Zhang, A.; Lieber, C.M. Nano-bioelectronics. Chem. Rev. 2016, 116, 215–257. [CrossRef] [PubMed] Herlin-Boime, N.; Sublemontier, O.; Lacour, F. Synthesis of Silicon Nanocrystals by Laser Pyrolysis. U.S. Patent 8337673 B2, 25 December 2012. Kang, Z.; Tsang, C.H.A.; Zhang, Z.; Zhang, M.; Wong, N.B.; Zapien, J.A.; Shan, Y.; Lee, S.T. A Polyoxometalate-assisted electrochemical method for silicon nanostructures preparation: From quantum dots to nanowires. J. Am. Chem. Soc. 2007, 129, 5326–5327. [CrossRef] [PubMed] Kang, Z.; Tsang, C.H.A.; Wong, N.B.; Zhang, Z.; Lee, S.T. Silicon quantum dots: A general photocatalyst for reduction, decomposition, and selective oxidation reactions. J. Am. Chem. Soc. 2007, 129, 12090–12091. [CrossRef] [PubMed] McVey, B.F.; Tilley, R.D. Solution synthesis, optical properties, and bioimaging applications of silicon nanocrystals. Acc. Chem. Res. 2014, 47, 3045–3051. [CrossRef] [PubMed] Tilley, R.D.; Warner, J.H.; Yamamoto, K.; Matsui, I.; Fujimori, H. Micro-emulsion synthesis of monodisperse surface stabilized silicon nanocrystals. Chem. Commun. 2005, 14, 1833–1835. [CrossRef] [PubMed] Hessel, C.M.; Reid, D.; Panthani, M.G.; Rasch, M.R.; Goodfellow, B.W.; Wei, J.; Fujii, H.; Akhavan, V.; Korgel, B.A. Synthesis of ligand-stabilized silicon nanocrystals with size-dependent photoluminescence spanning visible to near-infrared wavelengths. Chem. Mater. 2011, 24, 393–401. [CrossRef] Mangolini, L.; Thimsen, E.; Kortshagen, U. High-yield plasma synthesis of luminescent silicon nanocrystals. Nano Lett. 2005, 5, 655–659. [CrossRef] [PubMed] Mangolini, L.; Kortshagen, U. Plasma-assisted synthesis of silicon nanocrystal inks. Adv. Mater. 2007, 19, 2513–2519. [CrossRef] Gu, L.; Hall, D.J.; Qin, Z.; Anglin, E.; Joo, J.; Mooney, D.J.; Howell, S.B.; Sailor, M.J. In vivo time-gated fluorescence imaging with biodegradable luminescent porous silicon nanoparticles. Nat. Commun. 2013, 4, 2326. [CrossRef] [PubMed] Wang, J.; Liu, Y.; Peng, F.; Chen, C.; He, Y.; Ma, H.; Cao, L.; Sun, S. A General route to efficient functionalization of silicon quantum dots for high-performance fluorescent probes. Small 2012, 8, 2430–2435. [CrossRef] [PubMed] He, Y.; Zhong, Y.; Peng, F.; Wei, X.; Su, Y.; Lu, Y.; Su, S.; Gu, W.; Liao, L.; Lee, S.T. One-pot microwave synthesis of water-dispersible, ultraphoto and pH-stable, and highly fluorescent silicon quantum dots. J. Am. Chem. Soc. 2011, 133, 14192–14195. [CrossRef] [PubMed] Wu, S.C.; Zhong, Y.L.; Zhou, Y.F.; Song, B.; Chu, B.B.; Ji, X.Y.; Wu, Y.Y.; Su, Y.Y.; He, Y. Biomimetic preparation and dual-color bioimaging of fluorescent silicon nanoparticles. J. Am. Chem. Soc. 2015, 137, 14726–14732. [CrossRef] [PubMed] Nishimura, H.; Ritchie, K.; Kasai, R.S.; Goto, M.; Morone, N.; Sugimura, H.; Tanaka, K.; Sase, I.; Yoshimura, A.; Nakano, Y. Biocompatible fluorescent silicon nanocrystals for single-molecule tracking and fluorescence imaging. J. Cell Biol. 2013, 202, 967–983. [CrossRef] [PubMed] Atkins, T.M.; Cassidy, M.C.; Lee, M.; Ganguly, S.; Marcus, C.M.; Kauzlarich, S.M. Synthesis of long T1 silicon nanoparticles for hyperpolarized 29 Si magnetic resonance imaging. ACS Nano 2013, 7, 1609–1617. [CrossRef] [PubMed] Dasog, M.; De los Reyes, G.B.; Titova, L.V.; Hegmann, F.A.; Veinot, J.G. Size vs surface: tuning the photoluminescence of freestanding silicon nanocrystals across the visible spectrum via surface groups. ACS Nano 2014, 8, 9636–9648. [CrossRef] [PubMed]

Sensors 2017, 17, 268

42.

43.

44.

45. 46. 47.

48. 49. 50.

51.

52. 53.

54.

55. 56. 57.

58.

59. 60. 61.

14 of 15

Kehrle, J.; Hohlein, I.M.; Yang, Z.; Jochem, A.R.; Helbich, T.; Kraus, T.; Veinot, J.G.; Rieger, B. Thermoresponsive and photoluminescent hybrid silicon nanoparticles by surface-initiated group transfer polymerization of diethyl vinylphosphonate. Angew. Chem. Int. Ed. 2014, 53, 12494–12497. Zhai, Y.; Dasog, M.; Snitynsky, R.B.; Purkait, T.K.; Aghajamali, M.; Hahn, A.H.; Sturdy, C.B.; Lowary, T.L.; Veinot, J.G. Water-soluble photoluminescent D-mannose and L-alanine functionalized silicon nanocrystals and their application to cancer cell imaging. J. Mater. Chem. B 2014, 2, 8427–8433. [CrossRef] Li, Q.; Luo, T.Y.; Zhou, M.; Abroshan, H.; Huang, J.; Kim, H.J.; Rosi, N.L.; Shao, Z.; Jin, R. Silicon nanoparticles with surface nitrogen: 90% quantum yield with narrow luminescence bandwidth and the ligand structure based energy law. ACS Nano 2016, 10, 8385–8393. [CrossRef] [PubMed] Shabaev, A.; Hellberg, C.S.; Efros, A.L. Efficiency of multiexciton generation in colloidal nanostructures. Acc. Chem. Res. 2013, 46, 1242–1251. [CrossRef] [PubMed] Lu, X.T.; Hessel, C.M.; Yu, Y.X.; Bogart, T.D.; Korgel, B.A. Colloidal luminescent silicon nanorods. Nano Lett. 2013, 13, 3101–3105. [CrossRef] [PubMed] Song, B.; Zhong, Y.L.; Wu, S.C.; Chu, B.B.; Su, Y.Y.; He, Y. One-dimensional fluorescent silicon nanorods featuring ultrahigh photostability, favorable biocompatibility, and excitation wavelength-dependent emission spectra. J. Am. Chem. Soc. 2016, 138, 4824–4831. [CrossRef] [PubMed] Schmidt, V.; Wittemann, J.; Gosele, U. Growth, thermodynamics, and electrical properties of silicon nanowires. Chem. Rev. 2010, 110, 361–388. [CrossRef] [PubMed] Ma, D.; Lee, C.; Au, F.; Tong, S.; Lee, S. Small-diameter silicon nanowire surfaces. Science 2003, 299, 1874–1877. [CrossRef] [PubMed] Liu, L.; Peng, K.Q.; Hu, Y.; Wu, X.L.; Lee, S.T. Fabrication of silicon nanowire arrays by macroscopic galvanic cell-driven metal catalyzed electroless etching in aerated HF solution. Adv. Mater. 2014, 26, 1410–1413. [CrossRef] [PubMed] Hu, Y.; Peng, K.Q.; Qiao, Z.; Huang, X.; Zhang, F.Q.; Sun, R.N.; Meng, X.M.; Lee, S.T. Metal-catalyzed electroless etching of silicon in aerated HF/H2 O vapor for facile fabrication of silicon nanostructures. Nano Lett. 2014, 14, 4212–4219. [CrossRef] [PubMed] Sayed, S.Y.; Wang, F.; Malac, M.; Meldrum, A.; Egerton, R.F.; Buriak, J.M. Heteroepitaxial growth of gold nanostructures on silicon by galvanic displacement. ACS Nano 2009, 3, 2809–2817. [CrossRef] [PubMed] Peng, Z.; Hu, H.; Utama, M.I.B.; Wong, L.M.; Ghosh, K.; Chen, R.; Wang, S.; Shen, Z.; Xiong, Q. Heteroepitaxial decoration of Ag nanoparticles on Si nanowires: A case study on Raman scattering and mapping. Nano Lett. 2010, 10, 3940–3947. [CrossRef] [PubMed] Yi, Y.; Zhu, G.; Liu, C.; Huang, Y.; Zhang, Y.; Li, H.; Zhao, J.; Yao, S. A label-free silicon quantum dots-based photoluminescence sensor for ultrasensitive detection of pesticides. Anal. Chem. 2013, 85, 11464–11470. [CrossRef] [PubMed] Zhang, J.; Yu, S.-H. Highly photoluminescent silicon nanocrystals for rapid, label-free and recyclable detection of mercuric ions. Nanoscale 2014, 6, 4096–4101. [CrossRef] [PubMed] Zhao, J.N.; Deng, J.H.; Yi, Y.H.; Li, H.T.; Zhang, Y.Y.; Yao, S.Z. Label-free silicon quantum dots as fluorescent probe for selective and sensitive detection of copper ions. Talanta 2014, 125, 372–377. [CrossRef] [PubMed] Dhenadhayalan, N.; Lee, H.L.; Yadav, K.; Lin, K.C.; Lin, Y.T.; Chang, A.H. Silicon quantum dot-based fluorescence turn-on metal ion sensors in live cells. ACS Appl. Mater. Interfaces 2016, 8, 23953–23962. [CrossRef] [PubMed] Gonzalez, C.M.; Iqbal, M.; Dasog, M.; Piercey, D.G.; Lockwood, R.; Klapötke, T.M.; Veinot, J.G. Detection of high-energy compounds using photoluminescent silicon nanocrystal paper based sensors. Nanoscale 2014, 6, 2608–2612. [CrossRef] [PubMed] Ban, R.; Zheng, F.F.; Zhang, J.R. A highly sensitive fluorescence assay for 2,4,6-trinitrotoluene using amine-capped silicon quantum dots as a probe. Anal. Methods 2015, 7, 1732–1737. [CrossRef] Kim, J.S.; Cho, B.; Cho, S.G.; Sohn, H. Silicon quantum dot sensors for an explosive taggant, 2,3-dimethyl-2,3-dinitrobutane (DMNB). Chem. Commun. 2016, 52, 8207–8210. [CrossRef] [PubMed] Nguyen, A.; Gonzalez, C.M.; Sinelnikov, R.; Newman, W.; Sun, S.; Lockwood, R.; Veinot, J.G.; Meldrum, A. Detection of nitroaromatics in the solid, solution, and vapor phases using silicon quantum dot sensors. Nanotechnology 2016, 27, 105501. [CrossRef] [PubMed]

Sensors 2017, 17, 268

62.

63. 64. 65. 66. 67.

68. 69. 70.

15 of 15

Zhang, X.; Chen, X.; Kai, S.; Wang, H.Y.; Yang, J.; Wu, F.G.; Chen, Z. Highly sensitive and selective detection of dopamine using one-pot synthesized highly photoluminescent silicon nanoparticles. Anal. Chem. 2015, 87, 3360–3365. [CrossRef] [PubMed] Jose, A.R.; Sivasankaran, U.; Menon, S.; Kumar, K.G. A silicon nanoparticle based turn off fluorescent sensor for sudan I. Anal. Methods 2016, 8, 5701–5706. [CrossRef] Wang, G.; Yau, S.-T.; Mantey, K.; Nayfeh, M.H. Fluorescent Si nanoparticle-based electrode for sensing biomedical substances. Opt. Commun. 2008, 281, 1765–1770. [CrossRef] Yi, Y.H.; Deng, J.H.; Zhang, Y.Y.; Li, H.T.; Yao, S.Z. Label-free Si quantum dots as photoluminescence probes for glucose detection. Chem. Commum. 2013, 49, 612–614. [CrossRef] [PubMed] Lin, J.T.; Wang, Q.M. Role of novel silicon nanoparticles in luminescence detection of a family of antibiotics. RSC Adv. 2015, 5, 27458–27463. [CrossRef] Chu, B.B.; Wang, H.Y.; Song, B.; Peng, F.; Su, Y.Y.; He, Y. Fluorescent and photostable silicon nanoparticles sensors for real-time and long-term intracellular pH measurement in live cells. Anal. Chem. 2016, 88, 9235–9242. [CrossRef] [PubMed] Mu, L.; Shi, W.; Chang, J.C.; Lee, S.T. Silicon nanowires-based fluorescence sensor for Cu(II). Nano Lett. 2008, 8, 104–109. [CrossRef] Miao, R.; Mu, L.; Zhang, H.; She, G.; Zhou, B.; Xu, H.; Wang, P.; Shi, W. Silicon nanowire-based fluorescent nanosensor for complexed Cu2+ and its bioapplications. Nano Lett. 2014, 14, 3124–3129. [CrossRef] [PubMed] Su, S.; Wei, X.; Zhong, Y.; Guo, Y.; Su, Y.; Huang, Q.; Lee, S.T.; Fan, C.; He, Y. Silicon nanowire-based molecular beacons for high-sensitivity and sequence-specific DNA multiplexed analysis. ACS Nano 2012, 6, 2582–2590. [CrossRef] [PubMed] © 2017 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).