Analytica Chimica Acta 844 (2014) 54–60

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Non-labeling multiplex surface enhanced Raman scattering (SERS) detection of volatile organic compounds (VOCs) Chi Lok Wong a,1, U.S. Dinish a,1, Michael Stenbæk Schmidt b , Malini Olivo a,c, * a

Bio-optical Imaging Group, Singapore Bioimaging Consortium, Helios #01-02, 11 Biopolis Way, Singapore Department of Micro and Nanotechnology, Technical University of Denmark Ørsteds Plads, Building 345 East, DK-2800 Kongens Lyngby, Denmark c School of Physics, National University of Ireland, Galway, County Galway, Ireland b

H I G H L I G H T S

G R A P H I C A L A B S T R A C T


We report multiplex SERS based VOCs detection with leaning nanopillar substrate.
VOCs molecules adsorbed at the tip of the nano-pillars produce SERS signal.
Multiplex detection for the mixture of acetone and ethanol vapor is demonstrated.
To the best of our knowledge, it is the first SERS based multiplex VOCs detection.
The detection limits are 0.0017 ng (ethanol vapor) and 0.0037 ng (acetone vapor).

A R T I C L E I N F O

A B S T R A C T

Article history: Received 27 March 2014 Received in revised form 17 June 2014 Accepted 24 June 2014 Available online 27 June 2014

In this paper, we report multiplex SERS based VOCs detection with a leaning nano-pillar substrate. The VOCs analyte molecules adsorbed at the tips of the nano-pillars produced SERS signal due to the field enhancement occurring at the localized surface plasmon hot spots between adjacent leaning nanopillars. In this experiment, detections of acetone and ethanol vapor at different concentrations were demonstrated. The detection limits were found to be 0.0017 ng and 0.0037 ng for ethanol and acetone vapor molecules respectively. Our approach is a non-labeling method such that it does not require the incorporation of any chemical sensing layer for the enrichment of gas molecules on sensor surface. The leaning nano-pillar substrate also showed highly reproducible SERS signal in cyclic VOCs detection, which can reduce the detection cost in practical applications. Further, multiplex SERS detection on different combination of acetone and ethanol vapor was also successfully demonstrated. The vibrational fingerprints of molecular structures provide specific Raman peaks for different VOCs contents. To the best of our knowledge, this is the first multiplex VOCs detection using SERS. We believe that this work may lead to a portable device for multiplex, specific and highly sensitive detection of complex VOCs samples that can find potential applications in exhaled breath analysis, hazardous gas analysis, homeland security and environmental monitoring. ã 2014 Elsevier B.V. All rights reserved.

Keywords: Surface enhanced Raman scattering SERS Volatile organic compounds (VOCs) detection Multiplex detection Non-labeling

* Corresponding author at: Bio-optical Imaging Group, Singapore Bioimaging Consortium, Helios #01-02, 11 Biopolis Way, Singapore. E-mail address: [email protected] (M. Olivo). Joint first author.

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http://dx.doi.org/10.1016/j.aca.2014.06.043 0003-2670/ ã 2014 Elsevier B.V. All rights reserved.

C.L. Wong et al. / Analytica Chimica Acta 844 (2014) 54–60

1. Introduction Detection of volatile organic compounds (VOCs) has wide applications in health care (exhaled breath analysis) [1–3], chemical detection in industry [4,5], hazardous gas analysis [6], homeland security [7] and environmental monitoring [8]. Moreover, VOCs detection has great commercial importance. For example, miniaturized and low cost alcohols (ethanol) sensors find direct applications in the automotive industry, biofuel industry, the wine and spirits industry and food fermentation processes [5]. Acetone is also a common chemical that is extensively used in industrial and domestic applications, such as a solvent used in the printing industry and household products. Acetone vapor has been identified as a component of environmental tobacco smoke (ETS) and the adverse health effects have been reported in a number of surveys (10). In health care, exhaled breath analysis is a powerful tool for the diagnosis of various diseases [1– 3]. Exhaled acetone and ethanol concentration has been correlated to plasma glucose level [9] while exhaled acetone is also accepted as the breath biomarker for diabetes [3]. Gas chromatography and mass spectroscopy (GC–MS) is the most widely used technique for VOCs detection [1,10]. However, GC–MS is a bulky workstation and the physical dimension is not

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suitable for in-site detection applications outside the laboratory. Ion-mobility spectrometry (IMS) is another leading technique in chemical sensing [11,12]. Although, the measurement of portable mobility spectrometer is rapid and suitable for in-site detection, IMS is a destructive measurement method and complex VOCs sample (mixture) cannot be identified by this technique [11,12]. Raman spectroscopy is a versatile analytical tool because it reveals the vibrational fingerprints of molecular structures [13– 15]. Raman scattering cross sections are normally in the order of 1030 cm2 molecule1 sr1 and the low sensitivity has limited its practical application in VOCs detection [13]. Plasmonics sensing has gain rapid increasing research interests over the last decade [14–30]. Surface enhanced Raman scattering (SERS) employs metallic nanostructures that provides electromagnetic field enhancement at localized surface plasmon hot-spots and the resultant enhancement factor can be up to 1014 [13–15]. Single molecule detection has been demonstrated by SERS [31] and SERS has wide applications in analytical chemistry [32,33], biological detection [34–37] and environmental analysis [38,39]. However, only limited studies have been conducted in vapor-phase detection with SERS in the past two decade, while major research activities were on liquid-phase samples [13–15].

Fig. 1. (a) Scanning electron microscope (SEM) image of the nano-pillar substrate. (b) SEM image of the leaning nano-pillars after the evaporation of solvent. In each case, the leaning of the pillar and trapping of analyte molecule is schematically represented. (c) Schematic diagram of the multiplex SERS VOCs measurement platform.

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Fig. 2. (a) Reference spectrum captured before the injection of ethanol vapor (b) SERS spectrum of ethanol from the leaning nano-pillar substrate. Two signature peaks of ethanol vapor were clearly observed at 881 cm1 and 1454 cm1. (c) Control spectrum taken after the experiment, when the ethanol vapor was completely removed from the detection chamber.

Mosier-Boss et al. [40] reported the detection of the vapor of chlorinated solvents, methyl tert-butyl ether (MTBE) and aromatic compounds with enhanced Raman detection on roughened silver substrate. A thermoelectric cooler (TEC) based SERS system was used for vapor measurement. The experimental results showed that the majority of the Raman peaks of trichloroethylene (TCE) can only be observed when the substrate was cooled down to 5– 15  C. The requirement of temperature cooling limits the practical application and stability of SERS for VOCs detection. In addition, only VOCs (benzenethiol [41], 2,4-dinitrotoluene [42], pyridine [43] and 4-nitrophenol [43] vapor) with high Raman cross-section values have been detected [41–43]. In this paper, we propose the multiplex SERS based detection of VOCs using substrates that can generate high enhancement. The vibrational fingerprints of molecular structures provide specific Raman peaks for different VOCs analytes. To the best of our knowledge, this is the first demonstration of multiplex SERS detection of VOCs. Acetone and ethanol vapor with low Raman cross section are chosen as the model VOCs analytes, and their mixtures in different combination ratios have also been successfully identified in a multiplex format. To achieve high reproducibility and ‘metal-molecule-metal’ type hot spots to generate high enhancement, several substrate designs were reported in which analytes can be trapped in between the junction of metal nanowires or nanopillars/fingers [44–46]. In this context, we employed leaning pillar substrates fabricated on silicon (Si) by maskless dry etching [47] for the sensing of VOCs. Such a sensor will help in label free and direct detection of gases without the use of temperature cooling [40] and chemical sensing layer for molecular enrichment on sensor surface. This proposed technique can find promising potential applications in exhaled breath analysis, hazardous gas analysis,

Fig. 3. SERS spectra captured with the leaning nano-pillar substrate for the detection of (a) air (control) (b) ethanol vapor (5.3%) (c) 2.5% (d) 0.9% (e) 0.4%, (f) 0% (water vapor) concentration and (g) the linear relationship between the intensity of 880 cm1 peak in SERS spectra and concentrations of ethanol vapor.

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homeland security and environmental monitoring. It allows specific, multiplex and high sensitivity label free detection of complex VOCs samples, which cannot be achieved with current leading technique, ion-mobility spectrometry. 2. Experimental 2.1. Materials Analytical grade ethanol and acetone solution (EMD Millipore, USA) were used for the preparation of ethanol/acetone vapor in the experiment. For fabrication, the SERS substrates reactive ion etching (RIE) of undoped single side polished (1 0 0) silicon wafers was used. An Advanced Silicon Etcher (Surface Technology Systems MESC Multiplex ICP) was operated with a mixture of SF6 and O2 gases. Subsequently electron beam evaporation of silver was performed using an Alcatel SCM 600 at deposition rates of 10 Å s1 at a pressure of 2  106 mbar.

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grating (1800 lines mm1, spectral resolution of 0.7 cm1). The system was connected to the microscope (Leica) and a CCD detector. The laser was coupled through 50 objective lens (NA 0.40), which was also used to collect the Stokes-shifted Raman signal. Rayleigh scattering was blocked with a notch filter. The instrument was calibrated with the Raman signal from a silicon standard at 520 cm1. Baseline correction of the spectra was performed to remove the background and fluorescence band. 2.2. Procedures To investigate the performance of the SERS based VOCs detection platform, ethanol vapor and acetone vapors were chosen as the model analytes. For each analyte, cyclic detection was performed. It was followed with the detection of different concentration of vapor samples. Finally, the multiplex VOCs detection capability of the technique was demonstrated by the measurement of different combinations of ethanol and acetone vapor mixtures.

2.2. Apparatus 4. Results and discussion 2.2.1. Fabrication of the leaning nano-pillar substrate Using a novel maskless reactive ion etch process, we fabricate high aspect ratio silicon nanopillars and coat them with silver by electron beam evaporation. The maskless etch process is wafer scale, and as such is advantageous as it significantly reduces the processing time, allowing for the produced substrates to be used as cheap and expendable consumables. By fine tuning the ratio between the process gases SF6 and O2 gas ratios and adjusting the platen power accelerating the ion species towards the silicon wafer we are able to form nanopillars without using a lithographic step. These substrates exhibit a state of the art Raman enhancement over large areas (Fig. 1(a)) [47]. The novel aspect of this substrate design is that the aspect ratio of the pillars is so large that they are flexible and will lean towards their nearest neighbors when subjected to relatively weak forces. Prior to the sensing of VOCs, substrate is washed by dipping in pure ethanol and followed by drying in the Ar atmosphere to remove the impurities on the surface. During this cleaning process, once the solvent evaporates, surface tension will pull the nanopillars together and lean each other, thus creating self-assembled electromagnetic hot spots when illuminated by the laser (Fig. 1(b)). But before such leaned pillars are exposed to VOCs, we measured the spectra on bare substrate and ensured that there are no residual ethanol molecules contributing to the measured spectra from VOCs. Analyte molecules adsorbed at the surface of the pillars and also trapped in between the leaned pillars create an enormous number of hot spots inside the laser excited area. Enhancement factor (EF) of the nanopillar substrate was previously reported to be 106. This is based on the assumption that molecules adsorbed on the pillar and also trapped in the gap between the pillars are contributing to the EF. But if we assume that majority of the SERS enhancement is contributed by the molecules trapped between the pillars, then EF will be 1011 [47]. 2.2.2. SERS VOCs measurement Fig. 1(c) shows the schematic diagram of the multiplex SERS VOCs measurement platform. A mechanical pump was used to inject carrier gas into the bubbler chamber with ethanol, acetone or their mixture solutions. The saturated VOCs vapor was then fed into a gas chamber made of Telflon. As shown in Fig. 1(c), the leaning nano-pillar substrate was located inside the gas chamber and the transparent optical window on top of the substrate allowed the excitation and collection of SERS signal. SERS spectra were recorded using a Raman microscope (Renishaw inVia) with a 633 nm excitation laser source and equipped with a diffraction

4.1. Ethanol vapor detection A reference SERS spectrum was recorded with the substrate before it was exposed to ethanol vapor. As shown in Fig. 2(a), no significant peak was found in the spectrum. Ethanol vapor (5.3%) was then injected to the detection chamber for 1 min (at room temperature) and subsequently the SERS spectrum was acquired as shown in Fig. 2(b). Two sharp peaks at 881 cm1 and 1454 cm1 were observed and they matched very well with unenhanced

Fig. 4. Acetone vapor detection with leaning nano-pillars substrate (a) Reference spectrum captured before the injection of acetone vapor (b) SERS spectrum for acetone vapor detection. A signature peak of acetone vapor was clearly shown at 790 cm1. (c) Control spectrum taken when the acetone vapor has been removed from the detection chamber.

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Raman spectrum of ethanol solution (Fig. S1(a) Supplementary data). After that, the ethanol vapor inside the chamber was replaced by air and subsequently no ethanol SERS peak was observed (Fig. 2(c)). The same substrate was further applied for the detection of different concentrations of ethanol vapors. Fig. 3(a) shows the spectrum taken with air inside and before the injection of ethanol vapor. A series of ethanol vapor samples ranged from 5.3%, 2.5%, 0.9%, 0.4% and 0% (control – water vapor) were subsequently injected into the detection chamber. The corresponding SERS spectra are given in Fig. 3(b)–(f). To prevent contamination, the detection chamber was flushed with air in between each measurement. As shown in Fig. 3(b), the signature peak of ethanol vapor near 880 cm1 is clearly shown for 5.3% ethanol vapor. The peak intensity was found to decrease with ethanol vapor concentrations, which varied from 5.3 to 0.4% (Fig. 3(b)–(e)). The peak intensity variation is plotted in Fig. 3(g) and a linear response is observed. As shown in Fig. 3(b), the intensity of the ethanol signature peak (near 880 cm1) is 1930 intensity counts, which is the response of the SERS based VOCs sensing platform for ethanol vapor, while the measured standard deviation (e.g., SNR) in the spectrum is 66.6 intensity counts. For 5.3% ethanol vapor, the total mass of ethanol molecules within the laser spot (1 mm in diameter) is 0.048 ng. From Eq. (1), the detection limit of ethanol vapor is found to be 0.0017 ng (which is corresponding to 1815.1 ppm). Detail calculation steps are shown in Supplementary materials. Detection limit ¼

Mass of ethanol molecules  SNR Sensor response

(1)

4.2. Acetone vapor detection Acetone vapor was generated as described in Fig. 1(c) and the cyclic measurement results are provided in Fig. 4. As shown in Fig. 4(a), no significant peak was observed from the SERS substrate when air was filled in the detection chamber. Then, acetone vapor (25.4%) was injected to the detection chamber and a sharp peak at 791 cm1 was observed in the measured spectrum (Fig. 4(b)), which matches well with the Raman peak of acetone solution near 791 cm1 (Fig. S1(b) Supplementary materials). The low intensity peak located at 726 cm1 was caused by the substrate background signal at that particular location of the substrate. After that, the gas chamber was flushed with air and the acetone signature peak was not detected (Fig. 4(c)). Furthermore, detections at different concentrations of acetone vapors have been performed. Fig. 5(a) is the reference spectrum taken before the injection of acetone vapor and the SERS spectra of different concentrations of acetone vapor ranged from 24.5%, 10.3%, 3.5%, 0.8% and 0% (control – water vapor) are given in Fig. 5(b)–(f). For 24.5% acetone vapor, a sharp peak at 791 cm1 is shown (Fig. 5(b)) and the peak intensity is found to linearly increase with concentration of acetone vapor (Fig. 5(b)–(f)). The peak intensity variations are plotted for all concentrations and shown in Fig. 5(g). The detection limit for acetone vapor can be estimated from the spectrum of acetone vapor (25.4%) (Fig. 5(b)). The intensity of the acetone signature peak at 791 cm1 is 5660.9 intensity counts, while the measurement standard deviation of the baseline is 76.2 intensity counts. For 24.5% ethanol vapor, the total mass of acetone molecules in the laser spot is 0.223 ng. From Eq. (1), the detection limit of the SERS sensing platform for acetone vapor is found to be

Fig. 5. SERS spectra captured with the leaning nano-pillar substrate for the detection of (a) air (control) (b) acetone vapor (24.5%) (c) 10.3% (d) 3.5% (e) 0.8%, (f) 0% (water vapor) (g) The intensity variation of the 790 cm1 peak for different concentrations of the acetone vapor samples.

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increased correspondingly, however, the peak intensity of the acetone signature peak (791 cm1) was decreased in the spectra. In Fig. 6(e), only the 881 cm1 peak was observed in the SERS spectrum when ethanol vapor alone was fed in the detection chamber. The experimental results in Fig. 6(a)–(e) demonstrate the multiplex detection capability of the SERS based VOCs detection platform for different combinations of VOCs samples. To the best of our knowledge, it is the first multiplex VOCs detection based on SERS. The unique multiplex sensing feature allows specific and sensitive detection of particular or multiple VOCs analyte in a complex sample, which cannot be achieved with current leading technique such as, ion-mobility spectrometry.

5. Conclusions

Fig. 6. Multiplex detection of VOC samples with different concentrations of acetone and ethanol vapor.

0.0037 ng (which is corresponding to 3299.1 ppm). Detail calculation steps are shown in Supplementary materials. The experimental results presented in Figs. 2–5 have successfully demonstrated SERS based VOCs detection with the leaning nano-pillar substrate. Due to the exceptionally large enhancement of the Raman signal provided by the leaning nano-pillars structure, no temperature cooling and labeling sensing layer were required for the VOCs detection process, while in previous work [40], signature Raman peaks only appear at 5–15  C under complicated temperature cooling for roughened silver substrate. Reproducible SERS signals are also demonstrated in Fig. 2 and Fig. 4 for the cyclic detection of ethanol or acetone vapor. The re-usability of the nonlabeling leaning nano-pillar substrate can reduces the detection cost in practical usages. 4.3. Multiplex VOCs detection To demonstrate the multiplex detection capability of the SERS based VOCs detection platform, measurements on complex VOCs samples with different combinations of ethanol and acetone vapor mixtures have been performed. As shown in Fig. 6(a), only the acetone signature peak (791 cm1) was observed in the SERS spectrum when acetone vapor was fed on the substrate. After a flushing process, acetone–ethanol vapor mixture (17.3% acetone:1.6% ethanol) was injected to the detection chamber and the SERS spectrum is given in Fig. 6(b). It is found that the intensity of the acetone signature peak (791 cm1) decreases according to its reduced concentration, while the signature peak of ethanol (881 cm1) appears in the same SERS spectrum due to the ethanol vapor content. In Fig. 6(c) and (d), the ratio of ethanol vapor was further increased and the peak intensity of the 881 cm1 peak was

In this paper, we have demonstrated the multiplex VOCs detection using SERS. The VOCs analyte molecules adsorbed at the tips of the nano-pillars resulted in enhanced Raman signal due to the localized surface plasmon hot spots between adjacent leaning nanopillars. In the experiments, detections at different concentrations of acetone and ethanol vapor (VOCs with low Raman cross section values) have been demonstrated. The detection limits are found to be 0.0017 ng and 0.0037 ng for ethanol and acetone vapor molecules respectively. No temperature cooling was required in the VOCs detection process, while in previous work [40], signature Raman peaks only appear at 5–15  C with thiol modified roughened silver substrate. Moreover, our work demonstrates the label-free approach and hence no chemical sensing layer is required for molecule enrichment at hot spots on the substrates. The leaning nano-pillar substrate also show highly reproducible SERS signal in cyclic VOCs detection, which reduces the detection cost inpractical usages. To the best of our knowledge, it is the first multiplex VOCs detection based on SERS. In future, our work may lead to a portable device for multiplex, specific and highly sensitive detection of complex VOCs samples in exhaled breath analysis, hazardous gas analysis, homeland security and environmental monitoring.

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