WO2015026297A1 - Spectroscopic device, method of detecting surface-enhanced raman scattering (sers) signal, and method for multiplex detection of a plurality of volatile organic compounds using surface-enhanced raman scattering (sers) - Google Patents

Abstract

According to embodiments of the present invention, a spectroscopic device for surface-enhanced Raman scattering (SERS) is provided. The spectroscopic device includes a detection chamber including a window, and a SERS-active substrate arranged in the detection chamber, wherein the window is adapted to pass an excitation signal to illuminate the SERS-active substrate and further adapted to pass a SERS signal generated from the SERS-active substrate, and wherein the SERS-active substrate is arranged spaced apart from an inner surface of the window facing the SERS-active substrate by a spacing of about 0.4 mm or less. Further, a method of detecting surface-enhanced Raman scattering (SERS) signal associated with one or more volatile organic compounds and a method for multiplex detection of a plurality of volatile organic compounds using surface-enhanced Raman scattering (SERS) are also provided. Various embodiments may enable multiplex VOCs detection with SERS due to the multiplex detection feature of SERS.

Description

SPECTROSCOPIC DEVICE, METHOD OF DETECTING SURFACE-ENHANCED

RAMAN SCATTERING (SERS) SIGNAL, AND METHOD FOR MULTIPLEX DETECTION OF A PLURALITY OF VOLATILE ORGANIC COMPOUNDS USING SURFACE-ENHANCED RAMAN SCATTERING (SERS)

Cross-Reference To Related Application

reference in its entirety for all purposes.

Technical Field

[0002] Various embodiments relate to a spectroscopic device for surface-enhanced Raman scattering (SERS), a method of detecting surface-enhanced Raman scattering (SERS) signal and a method for multiplex detection of a plurality of volatile organic compounds using surface-enhanced Raman scattering (SERS). Further, various embodiments relate to SERS for volatile organic compounds (VOCs) detection and multiplex VOCs detection with SERS.

Background

[0003] Detection of volatile organic compounds (VOCs) has wide applications in health care (e.g. exhaled breath analysis), chemical detection in industry, hazardous gas analysis, homeland security and environmental monitoring. Moreover, VOCs detection has great commercial importance. For example, miniaturized and low cost alcohol (ethanol) sensors find direct applications in automotive industry, bio-fuel industry, and wine and spirits industry and food fermentation process. 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 fabrication. In environmental monitoring, acetone vapor has been identified as a component of environmental tobacco smoke (ETS) which causes a number of adverse health effects.

[0004] In health care, exhaled breath analysis is a powerful tool for the diagnosis of medical diseases. It is a non-invasive detection method and it is readily acceptable by patients. Sample collection is easy and even can be obtained from the unconscious - patients. VOCs (e.g. acetone, ethane, isoprene ethane, and pentane), inorganic gases (e.g. C0₂, H₂0₂) and non- volatile substances (e.g. isoprostanes, cytokines and nitrogen) are the common composition of human exhaled breath. VOCs and aerosolized particles are produced from the internal surface of lung, peripheral human cells and tissues, blood and bacteria or microorganisms. Carbon dioxide (C0₂), hydrogen peroxide (H₂0₂), acetone vapour and ethanol vapour are common breath disease biomarkers. Exhaled acetone and ethanol concentrations have been found to be correlated to plasma glucose level and exhaled acetone is also accepted as the breath biomarker for diabetes.

[0005] Gas chromatography and mass spectroscopy (GC-MS) and multi-detector gas chromatography system are by far the most common method for VOCs component and gas analysis. However, GC-MS is a bulky workstation and the physical dimension is not suitable for on-site detection applications outside the laboratory. Also, the cost of the system is high. Ion-mobility spectrometry (IMS) is another leading technique in chemical sensing for chemical vapor detection. 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.

[0006] Raman spectroscopy is a versatile analytical tool because it reveals the vibrational fingerprints of molecular structures and may be applied for VOCs mixture identification in Raman spectrum. Raman scattering cross sections are normally in the order of 10^"30 cm² molecule^"1 sr^"1 and the low sensitivity has limited its practical application in VOCs detection.

[0007] Plasmonics sensing has gained rapid increasing research interests over the last decade. Intensive research works have been conducted on surface plasmon enhanced detection, such as surface plasmon resonance (SPR), localized surface plasmon resonance (LSPR), surface plasmon field-enhanced fluorescence spectroscopy (SPFS) and surface plasmon-enhanced Raman scattering (SERS). Surface enhanced Raman scattering (SERS) employs metallic nanostructures that provide electromagnetic field enhancement at localized surface plasmon hot-spots and the resultant enhancement factor can be up to 10¹⁴. Single molecule detection has been demonstrated by SERS, which is considered as the ultimate limit of detection. SERS has wide applications in analytical chemistry, biological detection and environmental analysis. However, only limited studies have been conducted in vapor-phase detection with SERS in the past two decades, while major research activities were on liquid-phase samples.

[0008] The detection of the vapor of chlorinated solvents, methyl i-butyl ether (MTBE) and aromatic compounds with enhanced Raman detection on a roughened silver substrate had been reported, where 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, 2, 4- dinitrotoluene, pyridine and 4-nitrophenol vapor) with high Raman cross-section values have been detected.

Summary [0009] According to an embodiment, a spectroscopic device for surface-enhanced Raman scattering (SERS) is provided. The spectroscopic device may include a detection chamber including a window, and a SERS-active substrate arranged in the detection chamber, wherein the window is adapted to pass an excitation signal to illuminate the SERS-active substrate and further adapted to pass a SERS signal generated from the SERS-active substrate, and wherein the SERS-active substrate is arranged spaced apart from an inner surface of the window facing the SERS-active substrate by a spacing of about 0.4 mm or less.

[0010] According to an embodiment, a method of detecting surface-enhanced Raman scattering (SERS) signal is provided. The method may include arranging a SERS-active substrate in a detection chamber, spaced apart from an inner surface of a window of the detection chamber facing the SERS-active substrate by a spacing of about 0.4 mm or less, providing one or more volatile organic compounds to interact with the SERS-active substrate, illuminating the SERS-active substrate with an excitation signal provided through the window, and detecting a SERS signal passing through the window, the SERS signal being generated from the SERS-active substrate in response to the illumination by the excitation signal and the interaction with the one or more volatile organic compounds.

[0011] According to an embodiment, a method for multiplex detection of a plurality of volatile organic compounds using surface-enhanced Raman scattering (SERS) is provided. The method may include providing a plurality of volatile organic compounds to interact with a SERS-active substrate, illuminating the SERS-active substrate with an excitation signal, detecting a SERS signal generated from the SERS-active substrate in response to the illumination by the excitation signal and the interaction with the plurality of volatile organic compounds, and determining the respective identity of the plurality of volatile organic compounds from the detected SERS signal. Brief Description of the Drawings

[0012] In the drawings, like reference characters generally refer to like parts throughout the different views. The drawings are not necessarily to scale, emphasis instead generally being placed upon illustrating the principles of the invention. In the following description, various embodiments of the invention are described with reference to the following drawings, in which:

[0013] FIG. 1A shows a schematic cross-sectional view of a spectroscopic device for surface-enhanced Raman scattering (SERS), according to various embodiments.

[0014] FIG. IB shows a flow chart illustrating a method of detecting surface-enhanced Raman scattering (SERS) signal, according to various embodiments.

[0015] FIG. 1C shows a flow chart illustrating a method for multiplex detection of a plurality of volatile organic compounds using surface-enhanced Raman scattering (SERS), according to various embodiments.

[0016] FIGS. 2A to 2C shows scanning electron microscopy (SEM) images of a nano- pillar SERS substrate. [0017] FIG. 2D shows a scanning electron microscopy (SEM) image of a nano-gap SERS substrate.

[0018] FIG. 2E shows a schematic illustration of the sensing mechanism of the leaning nano-pillar substrate of FIGS. 2A to 2C.

[0019] FIG. 3 shows a schematic diagram of an optical sensing device of various embodiments.

[0020] FIG. 4A shows SERS spectra for cycling detection of ethanol vapour and air.

[0021] FIG. 4B shows SERS spectra for different concentrations of ethanol vapour generated from different ethanol solutions.

[0022] FIG. 4C shows a plot of the SERS intensity of the peak (879 cm^"1) for ethanol vapour generated from different concentrations of ethanol solutions.

[0023] FIG. 5 A shows SERS spectra for cycling detection of acetone vapour and air.

[0024] FIG. 5B shows SERS spectra for different concentrations of acetone vapour generated from different acetone solutions.

[0025] FIG. 5C shows a plot of the SERS intensity of the peak (790 cm^"1) for acetone vapour generated from different concentrations of acetone solutions.

[0026] FIG. 6 shows SERS spectra illustrating multiplex detection of VOC samples generated from different combinations of ethanol/acetone mixture.

[0027] FIG. 7 shows SERS spectra acetone vapour detection with a nano-gap SERS substrate.

[0028] FIG. 8 shows SERS spectra for cycling detection of ethanol vapour with a nano- gap substrate.

[0029] FIG. 9 shows a schematic diagram of an optical sensing device of various embodiments.

[0030] FIGS. 10A and 10B show the Raman spectra of an ethanol solution and an acetone solution, respectively.

[0031] FIG. 1 1 A shows SERS spectra for cyclic detection of ethanol vapour and air.

[0032] FIG. 1 IB shows SERS spectra for different concentrations of ethanol vapour.

[0033] FIG. l lC shows a plot showing the linear relationship between the intensity of the 880 cm^"1 peak in SERS spectra and the concentrations of ethanol vapour.

[0034] FIG. 12A shows SERS spectra for cyclic detection of acetone vapour and air. [0035] FIG. 12B shows SERS spectra for different concentrations of acetone vapour.

[0036] FIG. 12C shows a plot showing the linear relationship between the intensity of the 790cm^"1 peak in SERS spectra and the concentrations of acetone vapour.

[0037] FIG. 13 shows SERS spectra illustrating multiplex detection of VOC samples with different concentrations of acetone and ethanol vapours.

[0038] FIG. 14 shows a schematic diagram of an optical sensing device of various embodiments.

[0039] FIG. 15A shows SERS spectra for cyclic detection of acetone vapour and air.

[0040] FIG. 15B shows SERS spectra for different concentrations of acetone vapour.

[0041] FIG. 15C shows a plot showing the peak intensity variation of 790 cm^"1 peak with acetone vapour concentration.

[0042] FIG. 16 shows SERS spectra of the leaning nanopillar substrate and the bimetallic nanogap substrate for acetone vapor (24.5%) detection.

[0043] FIG. 17 shows a schematic diagram of an optical sensing device of various embodiments.

Detailed Description

[0044] The following detailed description refers to the accompanying drawings that show, by way of illustration, specific details and embodiments in which the invention may be practiced. These embodiments are described in sufficient detail to enable those skilled in the art to practice the invention. Other embodiments may be utilized and structural, logical, and electrical changes may be made without departing from the scope of the invention. The various embodiments are not necessarily mutually exclusive, as some embodiments can be combined with one or more other embodiments to form new embodiments.

[0045] Embodiments described in the context of one of the methods or devices are analogously valid for the other methods or devices. Similarly, embodiments described in the context of a method are analogously valid for a device, and vice versa.

[0046] Features that are described in the context of an embodiment may correspondingly be applicable to the same or similar features in the other embodiments. Features that are described in the context of an embodiment may correspondingly be applicable to the other embodiments, even if not explicitly described in these other embodiments. Furthermore, additions and/or combinations and/or alternatives as described for a feature in the context of an embodiment may correspondingly be applicable to the same or similar feature in the other embodiments.

[0047] In the context of various embodiments, the articles "a", "an" and "the" as used with regard to a feature or element include a reference to one or more of the features or elements.

[0048] In the context of various embodiments, the phrase "at least substantially" may include "exactly" and a reasonable variance.

[0049] In the context of various embodiments, the term "about" or "approximately" as applied to a numeric value encompasses the exact value and a reasonable variance.

[0050] As used herein, the term "and/or" includes any and all combinations of one or more of the associated listed items.

[0051] As used herein, the phrase of the form of "at least one of A or B" may include A or B or both A and B. Correspondingly, the phrase of the form of "at least one of A or B or C", or including further listed items, may include any and all combinations of one or more of the associated listed items.

[0052] Various embodiments may provide multiplex volatile organic compounds (VOCs) detection with surface enhanced Raman scattering (SERS).

[0053] Various embodiments may provide non-labeling multiplex surface enhanced Raman scattering (SERS) detection of volatile organic compounds (VOCs).

[0054] Various embodiments may provide a SERS based VOCs detection. The large enhancement of SERS compared to normal Raman (up to 10¹⁴) enables single molecule detection, which is considered to be the ultimate limit of detection. This technique also provides specific 'fingerprint' chemical information for multiplex detection of different VOCs compounds in the same spectrum. In various embodiments, ethanol vapour, acetone vapour and their mixtures have been employed as the VOCs analyte due to their aforementioned significances in automotive industry, bio-fuel industry, printing industry and health care. In addition, the SERS VOCs sensing technique may potentially become a handheld portable device for on-site VOCs detection. [0055] Various embodiments may provide a spectroscopic (sensing) device or an optical sensing device, which works on the principle of surface enhanced Raman scattering (SERS) spectroscopy and generates the fingerprint vibrational spectra of Volatile Organic Compounds (VOCs) molecules that may have very poor Raman activity. The sensor may be capable of generating SERS spectra of VOC molecules in a highly sensitive, cost effective and easier-label free approach with multiplexing capability. This sensor may be capable of detecting VOCs in a cyclic manner where the sensor surface is reusable and not contaminated. This sensor may be superior to existing expensive and cumbersome methodology that involves GC-MS (Gas chromatography- mass spectrometry). The sensor may be able to detect trace amount(s) of VOCs, which may be used in various applications that may include medical diagnostics, environmental monitoring, chemical sensing, home land security etc. This sensor may provide the best result compared to that obtained from prior art sensors in the field of SERS VOC Sensor.

[0056] The SERS VOCs detection of various embodiments may provide one or more of the following features:

[0057] (1) Multiplex SERS VOCs detection - Various embodiments may enable multiplex VOCs detection (e.g. ethanol-acetone mixture) using SERS together with a VOCs sensitive SERS-active substrate (e.g. VOCs sensitive nano-pillars SERS substrate, as will be described later); SERS is a "finger-print" detection technique and different VOCs gas samples have specific peaks distribution in the spectrum, and therefore different VOCs samples may be detected by SERS in a single spectrum.

[0058] (2) Non-labeling VOCs detection - Chemical sensing layers are required for existing VOCs sensors based on quartz crystal microbalance (QCM), surface plasmon resonance (SPR) and piezoelectric transducers (PZT). However, the SERS based VOCs detection of various embodiments is based on the Raman peak variations produced by plasmonic hot spot variations and no chemical sensing layer is required.

[0059] (3) Potential on-site SERS VOCs detection device - Existing gas chromatography (GC) and multi-detector gas chromatography system is a bulky workstation and the physical dimension is not suitable for on-site detection applications outside the laboratory. However, the SERS VOCs detection of various embodiments may potentially become a handheld portable device for on-site detection, which has wide applications in health care (exhaled breath analysis), chemical detection in industry, hazardous gas analysis, homeland security and environmental monitoring.

[0060] FIG. 1A shows a schematic cross-sectional view of a spectroscopic device 100 for surface-enhanced Raman scattering (SERS), according to various embodiments. The spectroscopic device 100 includes a detection chamber 1 10 including a window (e,g. an optical window) 1 12, and a SERS-active substrate 180 arranged in the detection chamber 110, wherein the window 1 12 is adapted to pass an excitation signal (e.g. an electromagnetic radiation or an optical excitation signal) 123 to illuminate the SERS- active substrate 180 and further adapted to pass a SERS signal (e.g. a SERS optical signal) 125 generated from the SERS-active substrate 180, and wherein the SERS-active substrate 180 is arranged spaced apart from an inner (or interior) surface of the window 1 12 facing the SERS-active substrate 180 by a spacing, d, of about 0.4 mm or less (e.g. < 0.4 mm). The SERS-active substrate 180 may be arranged coaxially with the window 1 12. In one or more embodiments, the term "SERS-active substrate" as used herein may include or may refer to a substrate that is configured to or capable of generating one or more SERS signals, e.g. SERS signal 125, in response to illumination of the substrate with an excitation signal, e.g. excitation signal 123, for example due to its surface configuration.

[0061] In various embodiments, the detection chamber 110 may be configured to receive at least one analyte for interaction with the SERS-active substrate 180 (e.g. come into contact with the SERS-active substrate 180). The at least one analyte may include at least one volatile organic compound (VOC), for example in vapour form.

[0062] In various embodiments, the SERS signal 125 may be generated from the SERS- active substrate 180 in response to the illumination the SERS-active substrate 180 by the excitation signal 123 and the interaction of the SERS-active substrate 180 with at least one analyte provided for interaction with the SERS-active substrate 180.

[0063] In the context of various embodiments, the spacing, d, may be between about 0.01 mm and about 0.4 mm, e.g. between about 0.01 mm and about 0.3 mm, between about 0.01 mm and about 0.2 mm, or between about 0.1 mm and about 0.2 mm, for example about 0.37 mm, or about 0.2 mm.

[0064] The spectroscopic device 100 may be a spectroscopic sensing device. [0065] The spectroscopic device 100 may be an optical spectroscopic device.

[0066] In various embodiments, the spectroscopic device 100 may further include an objective lens configured to focus the excitation signal 123 onto the SERS-active substrate 180 to illuminate the SERS-active substrate 180 and further configured to receive the SERS signal 125. The objective lens may be arranged outside the detection chamber 1 10. The objective lens may be arranged facing an outer (or exterior) surface of the window 1 12 of the detection chamber 110.

[0067] In the context of various embodiments, the objective lens may have a numerical aperture (NA) of about 0.75 or more (e.g. > 0.75), e.g. > 0.75, > 1, > 1.75, for example about 0.75, about 0.1 , or about 1,75.

[0068] In the context of various embodiments, the objective lens may have a magnification factor of 50 or more (e.g. > 50x), e.g. > 70x, > lOOx, for example about 50x, or about lOOx.

[0069] In various embodiments, the spectroscopic device 100 may further include an excitation source configured to generate the excitation signal 123. The excitation source may include a laser source. In various embodiments, the excitation signal 123 may have a wavelength, λ, of about 633 nm. This may mean that the laser source may be a 633 nm excitation laser source.

[0070] In various embodiments, the excitation signal 123 may be dimensioned to illuminate a spot size of about 1 μηι on the SERS-active substrate 180. This may mean that the excitation signal 123 may be a light beam or a laser beam to provide a beam size of a light or laser spot of about 1 μιη on the SERS-active substrate 180.

[0071] In various embodiments, the spectroscopic device 100 may further include a spectrometer configured to collect (or receive or detect) the SERS signal 125. The spectrometer may include a diffraction grating for spectrally dispersing the SERS signal 125.

[0072] In the context of various embodiments, the diffraction grating may have a line density of about 1800 lines/mm.

[0073] In the context of various embodiments, the diffraction grating may have a spectral resolution of about 0.7 cm^"1. [0074] In the context of various embodiments, the SERS-active substrate 180 may include a plurality of spaced-apart metallic nanostructures capable of generating hot-spots (e.g. plasmonic hot-spots) for generation of the SERS signal 125. In various embodiments, each hot spot may include an analyte molecule in direct contact with adjacent metallic nanostructures ('metal-molecule-metal' type hot spots).

[0075] In various embodiments, each metallic nanostructure may include at least one of silver (Ag) or gold (Au). For example, each metallic nanostructure may include a layer of silver (Ag), or a layer of gold (Au), or a layer of silver and a layer of gold arranged one over the other.

[0076] In various embodiments, the spectroscopic device 100 may further include a filter (e.g. a notch filter) configured to block transmission of Rayleigh scattering generated from the SERS-active substrate 180. The filter may be placed before the spectrometer.

[0077] In various embodiments, the spectroscopic device 100 may further include an arrangement of collimation optics for collimating the SERS signal 125. The arrangement of collimation optics may collimate the SERS signal 125 in a direction towards the spectrometer.

[0078] In various embodiments, the spectroscopic device 100 may further include a bubbler module for generating Vapour of at least one analyte (e.g. VOC) to be received by the detection chamber 110 for interaction with the SERS-active substrate 180. The bubbler module may include a pump for generating a carrier gas (e.g. air).

[0079] In various embodiments, the spectroscopic device 100 may further include a data processing unit configured to process data associated with the SERS signal 125. Non- limiting examples of processing may include at least one of recording the SERS signal 125, amplifying the SERS signal 125, or manipulating the data associated with the SERS signal 125. In various embodiments, the data processing unit may be coupled to the spectrometer. The data processing unit may be a computer.

[0080] In the context of various embodiments, the detection chamber 1 10 may be configured to receive one or more volatile organic compound (VOC) vapours for interaction with the SERS-active substrate 180 (e.g. the VOC vapour(s) may come into contact with the SERS-active substrate 180). The VOC may include at least one of ethanol, acetone or a non-aromatic compound. The VOC may have a low Raman cross- section value or weak Raman active molecules. In various embodiments, the detection chamber 1 10 may be configured to receive a plurality of volatile organic compound (VOC) vapours for interaction with the SERS-active substrate 180.

[0081] In the context of various embodiments, the SERS-active substrate 180 may be capable of interacting with respective vapours of one or more volatile organic compounds (VOCs) for generation of one or more respective SERS signals 125, where a respective SERS signal 125 may be associated with a respective VOC. In this way, a VOC may be identified based on or from an associated SERS signal 125.

[0082] In various embodiments, the spectroscopic device 100 may be free of a cooling device. For example, the spectroscopic device 100 may be free of a cooling device for cooling the SERS-active substrate 180. This may mean that the SERS-active substrate 180 may be maintained at room temperature in the detection chamber 110.

[0083] FIG. IB shows a flow chart 150 illustrating a method of detecting surface- enhanced Raman scattering (SERS) signal, according to various embodiments. The SERS signal may be associated with or correspond to at least one volatile organic compound (VOC).

[0084] At 152, a SERS-active substrate is arranged in a detection chamber, spaced apart from an inner surface of a window of the detection chamber facing the SERS-active substrate by a spacing of about 0.4 mm or less.

[0085] At 154, one or more volatile organic compounds (VOCs) are provided to interact with the SERS-active substrate. The VOC or VOCs may be provided into the detection chamber. The one or more VOCs may come into contact with the SERS-active substrate to interact with the SERS-active substrate. The one or more VOCs may be provided in vapour form, e.g. one or more VOC vapours may be provided to interact with the SERS- active substrate.

[0086] At 156, the SERS-active substrate is illuminated with an excitation signal provided through the window.

[0087] At 158, a SERS signal passing through the window is detected, the SERS signal being generated from the SERS-active substrate in response to the illumination by the excitation signal and the interaction with the one or more volatile organic compounds (VOCs). [0088] In various embodiments, at 154, a plurality of volatile organic compounds (VOCs) may be provided to interact with the SERS-active substrate. The plurality of VOCs may be provided in vapour form, e.g. a plurality of VOC vapours may be provided to interact with the SERS-active substrate.

[0089] In various embodiments, the method may further include identifying the one or more volatile organic compounds (VOCs) based on or from the detected SERS signal.

[0090] In various embodiments, the method may be performed at room temperature.

[0091] In various embodiments, the SERS-active substrate may be maintained at room temperature. For example, the SERS-active substrate may be at room temperature when the at least one analyte is provided to interact with the SERS-active substrate.

[0092] In the context of various embodiments, the spectroscopic device 100 and the method may be capable of detecting one or more VOCs or VOC vapours due to the multiplex feature of SERS. In the context of various embodiments, the spectroscopic device 100 and the method may be capable of detecting VOC or VOC vapours having low Raman cross-section values or weak Raman active molecules, for example at least one of ethanol vapour, acetone vapour or a non-aromatic compound vapour.

[0093] FIG. 1C shows a flow chart 170 illustrating a method for multiplex detection of a plurality of volatile organic compounds using surface-enhanced Raman scattering (SERS), according to various embodiments.

[0094] At 172, a plurality of volatile organic compounds (VOCs) are provided to interact with a SERS-active substrate. In various embodiments, each VOC may be provided in vapour form.

[0095] At 174, the SERS-active substrate is illuminated with an excitation signal.

[0096] At 176, a SERS signal generated from the SERS-active substrate in response to the illumination by the excitation signal and the interaction with the plurality of volatile organic compounds is detected.

[0097] At 178, the respective identity of the plurality of volatile organic compounds is determined from the detected SERS signal (e.g. which may be in the form of a single SERS spectrum).

[0098] In the context of various embodiments, the phrase "multiplex detection" as used above in relation to a plurality ofVOCs may mean simultaneous detection of the plurality of VOCs, for example based on a single SERS signal or a single spectrum. This may mean that different VOCs may be detected by SERS in a single spectrum.

[0099] Further, various embodiments may provide an optical spectroscopic sensing device having a laser light source, a standard Raman spectrometer, a SERS-active substrate, a gas detection chamber, and a detection mechanism or means including SERS that may generate label free fingerprint unique vibrational spectra of volatile organic compounds (VOCs). The sensing device may be capable of multiplex detection of trace amount of VOCs with its vibrational Raman spectra. The sensing device may further include a data processing unit being connected to the detecting mechanism and configured for processing data therefrom. The sensing device may be capable of detecting VOCs using SERS-active substrate having, for example nanostructured substrates made up of gold (Au), Silver (Ag) or its combination. The sensing device may be capable of detecting spectra in a total time of less than 30 seconds that may facilitate quick response time. The sensing device may be capable of detecting VOC spectra of weak Raman active molecules (e.g. ethanol, acetone, non-aromatic compounds, etc.). In various embodiments, the SERS-active substrate surface may be reversible and reproducible. Various embodiments may also provide a method of detecting VOC using the above- mentioned sensing device that may allow VOC molecules to be physisorbed onto the SERS-active substrate to generate fingerprint spectra.

[0100] Various embodiments will now be further described by way of the following non- limiting examples.

[0101] SERS substrates used in VOCs detection: Non-limiting examples of two different types of SERS-active substrates employed for multiplex VOCs detection with SERS may be as shown in FIGS. 2A to 2D. Nevertheless, it should be appreciated that other SERS- active substrates may also be employed.

[0102] FIGS. 2A to 2C shows scanning electron microscopy (SEM) images of a SERS- active substrate 200a having a plurality of nano-pillars (e.g. silicon nano-pillars) 202, while FIG. 2D shows a SEM image of a SERS-active substrate 200b having a plurality of nanostructures (e.g. silicon nanostructures) 204, for example in the form of nano-islands or nano-disks, with a nanogap between adjacent nanostructures 204, as indicated by the dashed box 206. Each nanostructure 204 may be coated with at least one metal (e.g. gold) The SERS-active substrate 200b may show an enhancement factor of approximately 10¹¹- 10¹³.

[0103] FIG. 2B shows a scanning electron microscopy (SEM) image of a side view of the nano-pillar SERS substrate 200a. The substrate 200a may include a plurality of nano- pillars 202 coated with silver (Ag). As shown in FIG. 2B, the tip of each nano-pillar 202 may be coated with silver 214. Further, the side surface of one or more nano-pillars 202 may also be coated with silver 215. In various embodiments, the aspect ratio of the nano- pillars 202 may be so large that they are flexible and may lean towards their nearest neighbors when subjected to relatively weak forces.

[0104] As a non-limiting example, the substrate 200a may be washed by dipping in pure ethanol and followed by drying in an argon (Ar) atmosphere to remove impurities on the surface. During this cleaning process, once the solvent evaporates, surface tension may pull the nano-pillars 202 together and lean to each other, thus creating self-assembled electromagnetic hot spots when illuminated by the laser. FIG. 2C shows a scanning electron microscopy (SEM) image of a top view of the leaning nano-pillars 202 after evaporation of solvent. The nano-pillars 202 may lean to each other in the manner as shown in FIG. 2E to be described below.

[0105] FIG. 2E shows the sensing mechanism of the leaning nano-pillar substrate 200a. The substrate 200a includes a plurality of nano-pillars 202 extending from a carrier 210 having a layer of metal (e.g. gold) 212. The nano-pillars 202 may be coated with a metal (e.g. gold) 214, for example at the tip of each nano-pillar 202 as shown in FIG. 2E, or covering each entire nano-pillar 202. When the gold coated silicon nano-pillars 202 are exposed to an analyte(e.g. one or more volatile organic compounds, VOCs), for example shown as 216, the surface tension may pull the nano-pillars 202 together and hot spots may be produced at the gap between the pillar surfaces. Some molecules, e.g. indicated as 216a, of the analyte may be captured in between adjacent leaning nano-pillars 202, in the hot spot, thereby producing 'metal-molecule-metal' type hot spots. This may lead to a tremendous enhancement of Raman signal, which may be used to detect analyte at low concentrations. In other words, when the nano-pillars 202 are exposed to analyte 216, the surface tension may pull the nano-pillars 202 together and an enhanced Raman signal may be produced in the hot spot ('metal-molecule-metal' type hot spots) at the nano-gap between the gold coated nano-pillars 202. In various embodiments, the substrate 200a having the plurality of nano-pillars 202 may be used for detecting one or more VOCs samples due to the multiplex feature of SERS.

[0106] FIG. 3 shows a schematic diagram of a spectroscopic device or an optical sensing device 300, e.g. a multiplex SERS VOCs measurement platform (or SERS VOCs detection system), of various embodiments. The optical sensing device 300 may include a bubbler chamber 304, which may receive a solution 306, e.g. an organic solvent. The bubbler chamber 304 may be coupled to a pump 302. The pump may provide or inject a carrier gas (e.g. air), for example via a tube 305, into the bubbler chamber 304 so as to generate bubbles within the solution 306. In this way, one or more vapours, such as volatile organic compound (VOC) vapour (e.g. ethanol vapour or acetone vapour or a mixture thereof) may be generated through a bubbling method. The VOCs vapour (as represented by arrows 360) produced may then be fed or guided, for example through a tube 308, into a chamber (e.g. a gas chamber or detection chamber) 310. The chamber 310 may be made of Teflon. A valve (e.g. a one-way valve) 340 may be provided to control the flow of the VOCs vapour 360 through the tube 308 towards and into the chamber 310.

[0107] Within the chamber 310, a SERS-active substrate 380 may be provided. It should be appreciated that any substrates capable of generating SERS signal may be used. In various embodiments, the SERS-active substrate 380 may be a SERS substrate having nanostructures for plasmonic hot-spot generation, including for example, the leaning nano-pillar substrate 200a or the nano-gap substrate 200b described above, which may provide enhanced SERS signals. The SERS-active substrate 380 may provide 'metal- molecule-metal' type hot spots for enhanced SERS signals.

[0108] The VOCs vapour 360 provided into the chamber 310 may interact with the SERS-active substrate 380 (e.g. come into contact with the SERS-active substrate 380), for example for detection of the VOCs vapour 360 using the SERS substrate 380. For example, molecules of the VOCs vapour 360 may be adsorbed (e.g. physisorbed) onto the SERS-active substrate 380. A non-limiting example of adsorption of the molecules of the VOCs vapour 360 may be as described in the context of FIG. 2E. [0109] The chamber 310 may include a window (e.g. an optical window) 312, which may be at least substantially transparent to allow at least a portion of an excitation signal (e.g. optical signal or light) to pass through. The optical window 312 may be arranged on the upper side (or upper portion) or the roof of the chamber 310. The optical window 312 may allow the excitation and collection of SERS signal from the substrate 380. The SERS sensitive substrate 380 may be arranged in the . chamber 310 coaxially with the optical window 312. The SERS substrate 380 may be arranged in the chamber 310, spaced apart from the window 312. For example, the SERS substrate 380 may be arranged at a distance, d, relative to the optical window 312. The distance, d, may be defined from the substrate 380 to the interior surface 31 1 of the optical window 312 which faces the substrate 380. As a non-limiting example, the distance, d, may be about 0.4 mm or less (e.g. < 0.4 mm), e.g. about 0.37 mm.

[0110] The VOCs vapour 360 may be removed from the chamber 310 via the tube 316 to a waste collector 318. A valve (e.g. a one-way valve) 342 may be provided to control the flow of the VOCs vapour 360 through the tube 316 towards the waste collector 318.

[0111] The optical sensing device 300 may include a laser source 322, which may provide an excitation signal or optical signal (as represented by arrows 323) for SERS excitation. The excitation light 323 may be directed through the optical window 312 and incident onto the SERS substrate 380 to illuminate at least a portion of the SERS substrate 380 for excitation of SERS signal. As a non-limiting example, the laser source 322 may be a 633 nm laser source, meaning that the excitation light 323 generated by the laser source 322 has a wavelength, λ, of about 633 nm. An objective lens 314 may be provided to focus the excitation light 323 onto the substrate 380. As a non-limiting example, the objective lens 314 may have a numerical aperture (NA) of 0.75 or more (e.g. > 0.75), e.g. about 0.75. As a non-limiting example, the objective lens 314 may have a magnification factor of at least 50x (e.g. > 50x), e.g. about 50x. In various embodiments, the beam size or diameter of the laser spot on the substrate 380 may be about 1 x 10^'6 m (1 μιη). For example, the objective lens 314 may confine the excitation light 323 to illuminate a 1 μιη excitation spot on the substrate 380.

[0112] SERS signal (or Raman signal) (as represented by arrows 325) that is generated upon interaction of the VOCs vapour 360 and the SERS-active substrate 380 and in response to excitation by the excitation light 323 may pass through the optical window 312 and collected through the objective lens 314. Therefore, the optical window 312 may allow the excitation laser beam 323 and the excited Raman signal 325 to pass through. Further, the objective lens 314 may be used for confinement of the laser beam 323 and collection of the SERS signal 325.

[0113] The SERS signal 325 may be collected using a Raman spectrometer 320. The Raman spectrometer 320 may include a diffraction grating having a line density of about 1800 lines/mm. The spectral resolution of the diffraction grating may be about 0.7 cm^"1. An arrangement of collimation optics 330 may be provided for collimation of the SERS signal 325. A reflector (e.g. a mirror) 332 may optionally be provided, for example for redirection of the optical path of the SERS signal 325 towards the Raman spectrometer 320. A Raman optical filter (e.g. a notch filter) 334 may be provided to minimise or block Rayleigh scattering which may originate from the substrate 380. A computer 326 may be provided for example to record the SERS signal 325. The computer 326 may also be used to manipulate or process the data coresponding to the SERS signal 325.

[0114] In various embodiments, the optical sensing device 300 may be capable of detecting VOC vapours having low Raman cross-section values or weak Raman active molecules, for example including but not limited to vapours of ethanol, acetone and non- aromatic compounds.

[0115] In various embodiments, the SERS substrate 380 may interact directly with the VOCs vapour 360. This may mean that the VOCs vapour 360 may remain in the vapour state during adsorption of the molecules of the VOCs vapour 360 onto the SERS substrate 380.

[0116] In various embodiments, the optical sensing device 300 may be free of any cooling means, for example free of any device which may provide cooling to the substrate 380. This may mean that there is no condensation of the VOCs vapour 360 into a liquid form prior to interaction with the substrate 380.

[0117] It should be appreciated that one or more of the parameters : numerical aperture (NA) of the objective lens 314, magnification factor of the objective lens 314, beam size of the laset spot on the substrate 380, distance, d, wavelength of the laser source 322, line density of the diffraction grating of the Raman spectrometer 320, or spectral resolution of the Raman spectrometer 320, may be provided or optimised so as to allow generation and collection of enhanced SERS signal 325 from the SERS-active substrate 380. In various embodiments, for optimisation, at least one of d = 0.37 mm, objective lens NA = 0.75, a SERS substrate having nanostructures for plasmonic hot-spot generation, or objective lens magnification factor = 50x may be provided to enable generation and collection of enhanced SERS signal for SERS VOCs detection.

[0118] SERS measurements with ethanol vapour and acetone vapour have been carried out to show the capability of SERS for VOCs detection, using the device 300 of FIG. 3.

[0119] VOCs detection with the nano-pillar SERS-active substrate (e.g. 200a, FIGS. 2A to 2C and 2E) will now be first described, by way of the following non-limiting examples.

[0120] Ethanol vapour detection: SERS measurements have been carried out for the cycling detection of ethanol vapour and air. The corresponding SERS spectra are shown in FIG. 4A. FIG. 4A shows a spectrum 400a when air is measured. When ethanol vapour is provided to the chamber 310 for detection, the spectrum 400b may be obtained with an observed sharp peak intensity at about 881cm^"1 from the ethanol vapour, which is in good agreement with the ethanol solvent spectrum as may be observed in FIG. 10A to be described later. As shown in the spectrum 400c, when the ethanol gas is replaced by air, the 881 cm^"1 peak disappears. The results show the specificity and the capability of the SERS technique for ethanol vapour detection.

[0121] In addition, different concentrations of ethanol vapour may be generated from different concentrations of ethanol solutions (e.g. 0%, 17.5%, 35%, 70% and 100%) for detection. Here, the different concentrations of the ethanol solutions refer to the percentage (%) of the ethanol solution, for example in the bubbler chamber 304 (FIG. 3). FIG. 4B shows the corresponding SERS spectra obtained for the detection of the different concentrations of vapour generated from the different ethanol solutions. The prominent ethanol peak at about 879 cm^"1 may be observed at all concentrations of ethanol vapour, as shown in the spectra 402b, 402c, 402d, 402e. However, as expected, it is not present in the control spectra of water, as shown in spectrum 402f and air, as shown in spectrum 402a. The arrows in spectra 402a, 402f indicate the position corresponding to a Raman shift value of about 879 cm^"1. In addition, the SERS intensity of the peak (879cm ¹) is found to be linearly dependent on the concentrations of the ethanol vapour, as shown in FIG. 4C, as illustrated for ethanol vapours generated from different concentrations of ethanol solutions (0%, 17.5%, 35%, 70% and 100%).

[0122] Acetone vapour detection: SERS detection for acetone vapour has also been carried out. FIG. 5A shows SERS spectra for cycling detection of acetone vapour and air, illustrating the cycling measurement results between saturated acetone VOC and air. In spectrum 500a, no acetone related peak may be observed when air is filled inside the gas chamber 310. However, a sharp peak at about 790 cm^"1 may be observed after the injection of acetone vapour onto the nano-pillars substrate surface (e.g. 380), as shown in spectrum 500b, which is correlated with the Raman peak of acetone at about 790 cm^"1 as may be observed in FIG. 10B to be described later. After that, the gas chamber 310 may be flushed with air and the 790 cm^"1 peak may no longer be observed, as shown in spectrum 500c. The arrows in spectra 500a, 500c indicate the position corresponding to a wavenumber value of about 790 cm^"1.

[0123] FIG. 5B shows SERS spectra for different concentrations of acetone vapour generated from different acetone solutions at 100%, 35%, 10% and 0% (water). Here, the different concentrations of the acetone solutions refer to the percentage (%) of the acetone solution, for example in the bubbler chamber 304 (FIG. 3). For acetone VOC generated from pure acetone, a sharp peak at about 790 cm^"1 may be observed and the peak intensity is about 5848 intensity counts, as shown in spectrum 502a. However, the peak intensity is decreased to about 2179 intensity counts when 35% acetone is applied, as shown in spectrum 502b. The peak intensity is further decreased to about 1025 intensity counts, as shown in spectrum 502c. The 790 cm^"1 peak may not be observed for the control experiment with water, as shown in spectrum 502d. The intensity of the 790 cm^"1 peak is found to be linear with the concentration (%) of the acetone samples applied, as shown in FIG. 5C.

[0124] Multiplex VOCs detection: SERS is a "finger-print" detection method and different VOCs samples have different spectral peaks distribution. SERS measurement for VOCs samples generated from different combinations of ethanol and acetone mixtures have been carried out and the results are shown in FIG. 6. As shown in spectrum 600a, the 791cm^"1 peak may be observed when acetone vapour is filled in the sample chamber 310. The intensity of the 791cm^"1 peak decreases with decreasing concentration of acetone VOC, while the intensity of 881 cm^"1 peak increases for increasing portion or concentration of ethanol in the VOC mixture, as shown in the spectra 600a, 600b, 600c, 600d, 600e. The 791cm^"1 peak finally disappears from the SERS spectrum when the ratio of acetone becomes zero, as shown in spectrum 600e. In FIG. 6, the different percentages (or concentrations) indicated for acetone and ethanol provide the ratios of acetone and ethanol in the acetone/ethanol mixture solution, for example in the bubbler chamber 304 (FIG. 3).

[0125] VOCs detection with the nano-gap SERS-active substrate (e.g. 200b, FIG. 2D) will now be described, by way of the following non-limiting examples.

[0126] The SERS VOCs detection has also been repeated with the nano-gap substrate. FIG. 7 shows SERS spectra for the cycling detection results of acetone vapour. The sample chamber 310 is filled with air and the spectrum 700a may be obtained. Acetone vapour may then be generated and injected into the sample chamber 310. The result shows that a ~790 cm^"1 SERS peak appears when acetone vapour fills the sample chamber 310, as shown in spectrum 700b. The sample chamber 310 may then be flushed with air and the spectrum 700c may be obtained. Acetone vapour may then be provided to fill the sample chamber 310 again and the spectrum 700d may be obtained, with an observable peak at about 790 cm^"1. The spectra 700b, 700d show that the ~ 790 cm^"1 SERS peak appears when acetone vapour fills the sample chamber. However, as shown in the spectra 700a, 700c, the SERS peak at about 790 cm^"1 disappears when the acetone gas is replaced by air.

[0127] The nano-gap substrate may also be applied for ethanol vapour detection. FIG. 8 shows SERS spectra for the cycling detection of ethanol vapour and air. A peak at about 880 cm^"1 may be observed in SERS spectrum 720b when ethanol vapour is injected to the sample chamber 310. No peak is observed at about 880cm^"1 prior to injection of the ethanol vapour into the sample chamber 310, as shown in spectrum 702a, while the peak at about 880cm^"1 disappears when the sample chamber 310 is flushed with air to remove the ethanol vapour.

[0128] Various embodiments and further results may be as described below by way of the following non-limiting examples. [0129] Various embodiments may provide a multiplex SERS based detection of VOCs using substrates that may generate high enhancement. The vibrational fingerprints of molecular structures may provide specific Raman peaks for different VOCs analytes. In various embodiments, as non-limiting examples, acetone and ethanol vapours with low Raman cross section may be used as the model VOCs analytes and their mixtures in different combination ratios have also been successfully identified in a multiplex format as will be described below.

[0130] In order to achieve high reproducibility and 'metal-molecule-metaP type hot spots to generate high enhancement, several substrate designs may be employed in which analytes may be trapped in between the junction of metal nanostructures (e.g. nanowires or nanopillars/fingers). In this context, leaning pillar substrates fabricated on silicon (Si) by maskless dry etching (e.g. substrate 200a, FIG. 2A) may be employed for the sensing of VOCs. Such a sensor may help in label free and direct detection of gases without the use of temperature cooling and chemical sensing layer for molecular enrichment on sensor surface. Such a technique may find promising potential applications in exhaled breath analysis, hazardous gas analysis, homeland security and environmental monitoring. It may allow specific, multiplex and high sensitivity label free detection of complex VOCs samples, which may not be achieved with current leading techniques, including ion-mobility spectrometry.

[0131] Various embodiments may provide multiplex SERS based VOCs detection with a leaning nano-pillaf substrate. VOCs analyte molecules may be adsorbed at the tips of the nano-pillars, which may produce SERS signal due to the field enhancement occurring at the localized surface plasmon hot spots between adjacent leaning nano-pillars. Detections of acetone and ethanol vapor at different concentrations may be carried out. The detection limits are found to be 0.0017ng and 0.0037ng for ethanol and acetone vapor molecules respectively as will be described below. The approach of various embodiments 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 shows highly reproducible SERS signal in cyclic VOCs detection, which may reduce the detection cost in practical applications. Further, multiplex SERS detection of different combinations of acetone and ethanol vapor may be performed as will be described below. The vibrational fingerprints of molecular structures provide specific Raman peaks for different VOCs contents. Various embodiments may lead to a portable device for multiplex, specific and highly sensitive detection of complex VOCs samples that may find potential applications in exhaled breath analysis, hazardous gas analysis, homeland security and environmental monitoring.

[0132] The fabrication and measurement procedures will now be described.

[0133] Materials: Analytical grade ethanol and acetone solution (EMD Millipore, USA) may be used for the preparation of ethanol/acetone vapor. For fabrication, the SERS substrates reactive ion etching (RIE) of undoped single side polished (100) silicon wafers may be used. An Advanced Silicon Etcher (Surface Technology Systems MESC Multiplex ICP) may be operated with a mixture of SF6 and O2 gases. Subsequently, electron beam evaporation of silver may be performed using an Alcatel SCM 600 at deposition rates of about 10 A/s at a pressure of about 2 x 10^"6 mbar.

[0134] Fabrication of the leaning nano-pillar substrate: Using a maskless reactive ion etch process, high aspect ratio silicon nanopillars may be fabricated and coated with silver (Ag) 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 0₂ gas ratios and adjusting the platen power accelerating the ion species towards the silicon wafer, nano-pillars may be formed without using a lithographic step. These substrates exhibit Raman enhancement over large areas. FIG. 2B shows a scanning electron microscopy (SEM) image of a side view of a nano-pillar SERS substrate 200a that may be obtained. The substrate 200a may include a plurality of nano-pillars 202 coated with silver (Ag). As shown in FIG. 2B, the tip of each nano-pillar 202 may be coated with silver 214. Further, the side surface of one or more nano-pillars 202 may also be coated with silver 215. In various embodiments, the aspect ratio of the nano-pillars 202 may be so large that they are flexible and may lean towards their nearest neighbors when subjected to relatively weak forces.

[0135] Prior to the sensing of VOCs, the substrate 200a may be washed by dipping in pure ethanol and followed by drying in an argon (Ar) atmosphere to remove impurities on the surface. During this cleaning process, once the solvent evaporates, surface tension may pull the nano-pillars 202 together and lean to each other, thus creating self- assembled electromagnetic hot spots when illuminated by the laser. FIG. 2C shows a scanning electron microscopy (SEM) image of a top view of the leaning nano-pillars 202 of FIG. 2B after evaporation of solvent. The nano-pillars 202 may lean to each other in the manner as shown in FIG. 2E. Before such leaned pillars may be exposed to one or more VOCs, a spectrum corresponding to the bare substrate may be measured to ensure that there are no residual ethanol molecules on the substrate that may contribute to the measured spectra from VOCs.

[0136] Analyte molecules adsorbed at the surface of the pillars 202 and also trapped in between the leaned pillars 202 may create an enormous number of hot spots inside the laser excited area, wchich may be as described above in the context of Fig. 2E. Enhancement factor (EF) of the nanopillar substrate may be about ~10⁶, based on the assumption that molecules adsorbed on the pillar and also trapped in the gap between the pillars contribute to the EF. However, assuming that the majority of the SERS enhancement is contributed by the molecules trapped between the pillars, then the EF may be ~ 10^{1 1}.

[0137] SERS VOCs measurement: FIG. 9 shows a schematic diagram of a spectroscopic device or an optical sensing device 900 of various embodiments, illustrating a multiplex SERS VOCs measurement platform. A mechanical pump 902 may be used to inject carrier gas into a bubbler chamber 904 with a solution 906, e.g. ethanol solution, or acetone solution or their mixture solutions. The saturated VOCs vapour produced may then be fed, for example through a tube 908, into a gas chamber 910 made of Teflon. As shown in FIG. 9, a leaning nano-pillar substrate 800 (e.g. 202, FIGS. 2A-2C) may be located inside the gas chamber 910 and the transparent optical window 912 provided through the gas chamber 910, on top of the substrate 800, may allow the excitation and collection of SERS signal from the substrate 800. The VOCs vapour may be removed from the gas chamber 910 via the tube 916 to a waste collector 918.

[0138] SERS spectra may be recorded using a Raman microscope (Renishaw InVia) 920 with a 633 nm excitation laser source 922 and equipped with a diffraction grating (1800 lines/mm, spectral resolution of ~ 0.7 cm^"1). The optical sensing device or system 900 may be connected to a microscope (Leica) and a CCD detector 924. A computer 926 may be provided to collect and record the data obtained, for example the SERS spectra.

[0139] The laser 922 may be coupled through a 50x objective lens (NA 0.40) 914, which may also be used to collect the Stokes-shifted Raman signal. Rayleigh scattering may be blocked with a notch filter (not shown), for example arranged in between the objective lens 914 and the Raman spectrometer 920. The device or instrument 900 may be calibrated with the Raman signal from a silicon standard at about 520 cm^-1. Baseline correction of the spectra may be performed to remove the background and fluorescence band.

[0140] The different components or features of the sensing device 900, including parameters, may be as described above in the context of the sensing device 300 (FIG. 3).

[0141] In order to investigate the performance of the SERS based VOCs detection platform, ethanol vapour and acetone vapour may be chosen as the model analytes. For each analyte, cyclic detection may be performed. It may be followed by the detection of different concentrations of vapour samples. Further, the multiplex VOCs detection capability of the technique may be demonstrated by the measurement of different combinations of ethanol and acetone vapour mixtures. For comparison purposes, Raman spectra corresponding to an ethanol solution and an acetone solution are shown in FIGS. 10A and 10B, respectively.

[0142] Ethanol vapour detection: FIG. 11A shows SERS spectra for cyclic detection of ethanol vapour and air. A reference SERS spectrum may be recorded with the substrate 800 before it is exposed to ethanol vapour. As shown in spectrum 1 100a captured before the injection of ethanol vapour, no significant peak may be found in the spectrum 1100a. Ethanol vapour (5.3%) may then be injected to the detection chamber 910 for about 1 minute (at room temperature) and subsequently the SERS spectrum of ethanol from the leaning nano-pillar substrate 800 may be acquired, as shown in spectrum 1 100b. Two signature sharp peaks of ethanol vapour may be clearly observed at 881cm^"1 and 1454cm^"1, which match very well with the un-enhanced Raman spectrum of an ethanol solution as shown in FIG. 1 OA. After that, a control spectrum may be taken, where the ethanol vapour inside the chamber 910 may be replaced by air, thereby completely removing the ethanol vapour from the detection chamber 910. As shown in spectrum 1 100c, no ethanol SERS peak may be observed.

[0143] The same substrate 800 may be further applied for the detection of different concentrations of ethanol vapours. FIG. 1 IB shows SERS spectra for different concentrations of ethanol vapour, illustrating the SERS spectra captured with the leaning nano-pillar substrate 800 for the detection of air (control), ethanol vapour at different concentrations (5.3%, 2.5%, 0.9%, 0.4%) and at 0% (water vapour) concentration.

[0144] Fig. 1 IB shows spectrum 1 102a taken with air inside the chamber 910 and before the injection of ethanol vapour. A series of ethanol vapour samples at about 5.3%, 2.5%, 0.9%%, 0.4% and 0% (control - water vapour) may subsequently be injected into the detection chamber 910. Here, the different concentrations of the ethanol vapours refer to the percentage (%) of the ethanol vapour in the VOC sample provided into the chamber 910. The corresponding SERS spectra may be as shown by spectra 1 102b, 1102c, 1102d, 1 102e, 1 102f. To prevent contamination, the detection chamber 910 may be flushed with air in between two measurements. As shown in spectrum 1 102b, the signature peak of ethanol vapour near about 880cm^"1 is clearly shown for 5.3% ethanol vapour. The peak intensity is found to decrease with ethanol vapour concentrations decreasing from about 5.3% to about 0.4%. FIG. 1 1C shows a plot showing the linear relationship (or linear response) between the intensity of the 880cm^"1 peak in SERS spectra and the concentrations of ethanol vapour. The results shown in FIGS. 1 IB and l lC may correspond to the results shown in FIGS. 4B and 4C.

[0145] The detection limit calculation of the SERS VOCs measurement sensor platform corresponding to ethanol vapor detection may be as described below. The detection limit may be determined using the following equation:

^ ^■ , ^ Mass of ethanol molecules ^ _t- Detection Limit = χ SNR (Equation 1),

Sensor response

where SNR is the signal to noise ratio of the Raman spectrum.

[0146] As shown in spectrum 1 102b (FIG. 1 IB) corresponding to 5.3% ethanol vapour, the intensity of the ethanol signature peak (near 880cm^"1) is about 1930 intensity counts, which is the "Sensor response" of the SERS based VOCs sensing platform for ethanol vapour. Further, the measurement standard deviation (S.D.) of the control Raman spectrum (recorded for water vapor) is about 66.6 intensity counts (spectrum 1 102f, FIG. 1 1B), which is considered as the SNR value. The mass of the ethanol molecules may be determined as follows:

Total mass of ethanol molecules = Volume x Density (Equation 2).

[0147] During SERS detection, the diameter of the laser spot is about 1 μιη. Furthermore, the gap between the SERS substrate 800 and the glass optical window of the gas chamber 910 is about 0.37 mm. Therefore, Equation 2 may be modified as:

Total mass of ethanol molecules = {nr ^~h)x. Density (Equation 3)

= ^(l0^"6 )² (0.00037)w³ x 0.789g / c/w³

= 0.917 χ 1(Γ⁹ £ .

[0148] The saturation vapor pressure of ethanol vapor at 20°C is about 5.26% (40 mm/Hg). The effective mass of ethanol molecules may therefore be determined as (0.917 x 10^"9g x 5.26% = 0.048 ng). Accordingly, for about 5.3% ethanol vapour, the total mass of ethanol molecules within the laser spot (1 μηι in diameter) is about 0.048 ng.

[0149] From Equation 1 ,

Detection Limit = - ^ⁿS— _x 66. ecou/ite = 0.0017«g■

\ 930counts

[0150] Accordingly, the detection limit of ethanol vapor measurement with the sensing device or system of various embodiments is found to be approximately 0.0017 ng.

[0151] The detection limit may also be calculated in the unit of ppm, as shown below:

„ Concentration of ethanol vapour „, _/x, .. _Λ^

Detection Limit = - — x SNR (Equation 4)

Sensor response

52600 ppm

= — x ob.bcounts

\930counts

= \S l5 Appm .

[0152] Acetone vapour detection: Acetone vapour may be generated as described above in the context of FIG. 9 and the cyclic measurement results may be as shown in FIG. 12A. A reference spectrum may be captured before the injection of acetone vapour into the chamber 910. As shown in spectrum 1200a, no significant peak may be observed from the SERS substrate when air is filled into the detection chamber 910. Then, acetone vapour (approximately 25.4%) may be injected into the detection chamber 910 and a signature sharp peak at about 791 cm^"1 may be observed in the measured spectrum 1200b, which matches well with the Raman peak of acetone solution near 791 cm^"1 as shown in FIG. 10B. A low intensity peak located at about 726 cm^"1 may be caused by the substrate background signal at that particular location of the substrate 800. After that, a control spectrum may be taken, where the acetone vapour inside the chamber 910 is removed from the detection chamber 910 by flushing with air. As shown in spectrum 1200c, no acetone signature peak may be detected.

[0153] Further, detections at different concentrations of acetone vapours may be performed. FIG. 12B shows SERS spectra for different concentrations of acetone vapour, illustrating the SERS spectra captured with the leaning nano-pillar substrate 800 for the detection of air (control), acetone vapour at different concentrations (24.5%, 10.3%, 3.5%, 0.8%) and at 0% (water vapour) concentration. Here, the different concentrations of the acetone vapours refer to the percentage (%) of the acetone vapour in the VOC sample provided into the chamber 910.

[0154] Fig. 12B shows a reference spectrum 1202a taken before the injection of acetone vapour into the chamber 910. A series of acetone vapour samples at about 24.5%, 10.3%, 3.5%, 0.8% and 0% (control - water vapour) may subsequently be injected into the detection chamber 910. The corresponding SERS spectra may be as shown by spectra 1202b, 1202c, 1202d, 1202e, 1202f. To prevent contamination, the detection chamber 910 may be flushed with air in between two measurements. As shown in spectrum 1202b for 24.5% acetone, a sharp peak at about 791 cm^"1 may be observed. The peak intensity is found to linearly increase with an increase in the concentration of acetone vapour. FIG. 12C shows a plot showing the intensity variation of the 790 cm^"1 peak for different concentrations of the acetone vapour samples. The results shown in

FIGS. 12B and 12C may correspond to the results shown in FIGS. 5B and 5C.

[0155] The detection limit calculation of the SERS VOCs measurement sensor platform corresponding to acetone vapor detection may be as described below. The detection limit may be determined using the following equation:

. Mass of acetone molecules ,_r ..

Detection Limit = x SNR (Equation 5),

Sensor response where SNR is the signal to noise ratio of the Raman spectrum.

[0156] As shown in spectrum 1202b (FIG. 12B) corresponding to 24.5% acetone vapour, the intensity of the acetone signature peak at about 791cm^"1 is about 5661 intensity counts, which is the "Sensor response" of the SERS based VOCs sensing platform for acetone vapour. Further, the measurement standard deviation (S.D.) of the control Raman spectrum (recorded for water vapor) is about 76.23 intensity counts (spectrum 1202f, FIG. 12B), which is considered as the SNR value. The mass of the acetone molecules may be determined as follows:

Total mass of acetone molecules = Volume x Density (Equation 6).

[0157] During SERS detection, the diameter of the laser spot is about 1 μηι. Furthermore, the gap between the SERS substrate 800 and the optical window of the gas chamber 910 is about 0.37 mm. Therefore Equation 6 may be modified as:

Total mass of acetone molecules = { ~²h)x Density (Equation 7)

= πτ(ΐ0^"6 )² (0.00037 )m ³ x 0.791g / cm³

= 0.911 x l0^~9 g .

[0158] The saturation vapor pressure of acetone vapor at 20°C is about 24.5% (186 mm/Hg). The effective mass of acetone molecules inside the laser spot may therefore be determined as (0.91 1 x 10^"9g x 24.5% = 0.223 ng). Accordingly, for about 24.5% acetone vapour, the total mass of acetone molecules in the laser spot (1 μηι in diameter) is about 0.223 ng.

[0159] From Equation 5,

0.223ng

Detection Limit = x 76.23counts = 0.0037«g ·

566lcounts

[0160] Accordingly, the detection limit of acetone vapor measurement with the sensing device or system of various embodiments is found to be approximately 0.0037 ng.

[0161] The detection limit may also be calculated in the unit of ppm, as shown below:

Concentration of acetone vapour „, _T„ _T- .. _ΟΛ

Detection Limit = x SNR (Equation 8)

Sensor response

245000 ppm ^■„.,

= —— x /6.23counts

566\counts

= 3299 λρρτη . [0162] The results presented in FIGS. 1 1A-1 1C and 12A-12C have successfully demonstrated SERS based VOCs detection with the leaning nano-pillar substrate 800. Due to the exceptionally large enhancement of the Raman signal provided by the leaning nano-pillars structure 800, no temperature cooling and labelling sensing layer may be required for the VOCs detection process, while in a prior art method, signature Raman peaks only appear at 5-15 C under complicated temperature cooling for thiol modified roughened silver substrates. Reproducible SERS signals are also demonstrated in FIGS. 1 1A and 12A for the cyclic detection of ethanol vapour or acetone vapour. The reusability of the non-labelling leaning nano-pillar substrate 800 may reduce the detection cost in practical usages.

[0163] Multiplex VOCs detection: In order 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 vapour mixtures may be performed. FIG. 13 shows SERS spectra illustrating multiplex detection of VOC samples with different concentrations of acetone and ethanol vapours. In FIG. 13, the different percentages (or concentrations) indicated for acetone and ethanol provide the ratios of acetone vapour and ethanol vapour in the VOCs sample provided into the chamber 910. As shown in spectrum 1300a, only the acetone signature peak (791 cm^'1) may be observed in the SERS spectrum 1300a when acetone vapour is fed onto the substrate 800. After a flushing process with air, acetone-ethanol vapour mixture (17.3% acetone: 1.6% ethanol) may be injected to the detection chamber 910 and the. SERS spectrum 1300b may be obtained. It may be observed that the intensity of the acetone signature peak (791 cm^"1) decreases according to its reduced concentration, while the signature peak of ethanol (881 cm^"1) appears in the same SERS spectrum 1300b due to the ethanol vapour content. In spectra 1300c and 1300d, the ratio of the ethanol vapour has been further increased and the peak intensity of the 881 cm^"1 peak has increased correspondingly, however the peak intensity of the acetone signature peak (791 cm^"1) is decreased in the spectra 1300c, 1300d. In spectrum 1300e, only the 881 cm^'1 peak may be observed in the SERS spectrum 1300e when ethanol vapour alone is fed into the detection chamber 910. The results shown in FIG. 13 may correspond to the results shown in FIG.6. The results shown in FIG. 13 desmonstrate the multiplex detection capability of the SERS based VOCs detection platform for different combinations of VOCs samples. 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 techniques such as, for example, ion-mobility spectrometry.

[0164] As described above, multiplex VOCs detection using SERS has been shown. The VOCs analyte molecules adsorbed at the tips of the nano-pillars may result in enhanced Raman signal due to the localized surface plasmon hot spots between adjacent leaning nano-pillars. Detections at different concentrations of acetone and ethanol vapor (VOCs with low Raman cross section values) have been shown. The detection limits are found to be approximately 0.0017 ng and 0.0037 ng for ethanol and acetone vapor molecules respectively. No temperature cooling may be required in the VOCs detection process. Moreover, various embodiments demonstrate a label-free approach and hence no chemical sensing layer may be 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 may reduce the detection cost in practical usages. Various embodiments 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.

[01651 Various embodiments may also provide surface enhanced Raman scattering (SERS) based volatile organic compounds (VOCs) detection using plasmonic bimetallic nano-gap substrate. In various embodiments, the bimetallic nano-gap structure substrate may be fabricated using deep UV photolithography (DUV) at a wavelength of about 250 nm to pattern circular shape nanostructures on a silicon wafer to form the nano-gap SERS-active substrate. The nano-gap between adjacent circular patterns may be about 30nm ± 5nm. Silver (Ag) (thickness of about 30 nm) and gold (Au) (thickness of about 15 nm) plasmonic active layers may be deposited on the nanostructures subsequently. SERS measurements of different concentrations of acetone vapor at about 0.7%, 1.5%, 3.5%, 10.3%), 24.5% and control may be performed with the substrate. The measurement results have been found to be reproducible and the detection limit is found to be about 9.5 pg (acetone molecule) as will be described later below. The detection sensitivity is approximately 28.7% higher as compared to other suibstrates, for example the leaning silicon nano-pillars substrate which itself provides 620 times larger Raman signal compared to commercially available substrates. With further system miniaturization, the sensing technique may work as a portable SERS based VOCs detection platform for point-of-care breath analysis, homeland security, chemical sensing and environmental monitoring.

[0166] The fabrication and measurement procedures will now be described.

[0167] Fabrication of bimetallic nanogap plasmonic nanostructure: Deep UV photolithography (DUV) at a wavelength of 250nm may be used to pattern nanostructures on an 8-inch diameter single crystal p-type Si wafer. In the lithography process, a positive photo-resist of a 41 ooA thick may be applied. It is followed with a baking step (at about 130°C for about 90 seconds) and the puddle development process. A single binary mask with circular patterns may be used to generate different sizes of nano-gap structures by varying the exposure dosage from about 66, 70, 74 to about 78mJ/cm². Deep reactive ion etching system may be used in silicon etching with SF₆ and C₄F₈ chemistry and the etching depth may be about 150nm. The spacing of the nanostructure may be controlled by dry oxidation at about 900°C for about 2 - 6 hours. Then, Ag (about 30 nra thick) and Au (about 15 nm thick) plasmonic active layers may be deposited subsequently on the nanostructures by e-beam evaporation. The bimetallic nanogap plasmonic nanostructure fabricated may be as shown in FIG. 2D.

[0168] Measurement set-up: FIG. 14 shows a schematic diagram of a spectroscopic device or an optical sensing device 1400 of various embodiments. The optical sensing device 1400 may include a mechanical pump 1402 for injecting a carrier gas (e.g. air) into a bubbler chamber 1404 with a solution 1406, e.g. acetone solution. The acetone vapour produced may then be fed, for example through a tube 1408, into a gas or detection chamber 1410. As shown in FIG. 14, a nano-gap substrate 1480 (e.g. substrate 200b, FIG. 2D) may be located inside the chamber 1410. While not shown, a window (e.g. transparent optical window) may be provided through the chamber 1410, over the top of the substrate 1480 to allow the excitation and collection of SERS signal from the substrate 1480 through the window. The acetone vapour may be removed from the chamber 1410 via the tube 1416 to a waste collector 1418. [0169] Different concentrations of acetone vapor (e.g. about 0.7%, 1.5%, 3.5%, 10.3% and 24.5%) may be generated with the bubbling system 1404. During detection, the bimetallic nano-gap substrate 1480 may be placed in the detection chamber 1410. Excitation light from a He-Ne laser (wavelength, λ = 633nm) 1422 may be incident on the Ag-Au coated nanostructures of the substrate 1480 through an objective lens (50x, 0.75 N.A.) 1414. The laser spot may be approximately 1 μιη in diameter and the SERS spectrum may be recorded by a commercial Raman spectrometer (Renishaw In Via) 1420. A CCD detector 1424 may also be provided.

[0170] The different components or features of the sensing device 1400, including parameters, may be as described above in the context of the sensing device 300 (FIG. 3) and/or the sensing device 900 (FIG. 9).

[0171] In order to demonstrate SERS based VOCs detection with the bimetallic nano-gap substrate 1480, measurement using acetone vapor at 24.5% may be performed. A reference spectrum may first be recorded when the detection chamber 1410 is filled with air, before the injection of acetone vapour. FIG. 15A shows spectrum 1500a that may be obtained, indicating that no significant peak may be observed in the spectrum 1500a. Acetone vapor (24.5%) may then be injected into the chamber 1410 and the SERS signal generated with the bimetallic nano-gap nanostructure of the substrate 1480 may be as shown in spectrum 1500b. A significant peak is found at about 790 cm^"1, which is correlated to the Raman signature peak of acetone at 790 cm^"1 as shown in FIG. 10B. A control spectrum (air) may be taken after the flushing process of the bimetallic nanogap nanostructure surface of the substrate 1480 by flushing the chamber 1410 with air. As shown in spectrum 1500c, no significant peak may be observed. The cycling detection results of FIG. 15A reveal the reproducibility of the technique for VOCs detection.

[0172] Measurements for different concentrations of acetone vapor at about 24.5%, 10.3%, 3.5%, 1.5%, 0.7% have further been performed and the results are shown in FIG. 15B. The acetone signature peak (at about 790 cm^"1) is clearly seen in spectrum 1502a when 24.5% acetone vapor is injected to the detection chamber 1410. Then, the detection chamber 1410 may be flushed with air in order to remove the acetone molecules from the nanogap substrate surface before the next measurement. FIG. 15B further show the corresponding spectra 1502b, 1502c, 1502d, 1502e obtained when acetone vapour at concentrations of about 10.3%, 3.5%, 1.5% and 0.7%, respectively, are provided to the chamber 1410. As shown in spectra 1502b, 1502c, 1502d, 1502e, the acetone signature peak (790 cm^"1) is observed for 10.3%, 3.5%, 1.5% and 0.7% acetone vapor. After that, the detection chamber 1410 may be flushed with air and a control SERS spectrum may be recorded, as shown by spectrum 1502f. As may be observed in spectrum 1502f, the 790cm^"1 peak corresponding to acetone is not found in the control spectrum 1502f.

[0173] FIG. 15C shows a plot showing the peak intensity variation of 790 cm^"1 peak with acetone vapour concentration, illustrating the response curve of the sensing device or platform 1400 for acetone vapor detection. A direct proportional relationship between the peak intensity and the acetone vapor concentration may be found.

[0174] The detection limit of the SERS VOCs system may be estimated using Equation 5 described above. The term "SNR" may also be known as "baseline variation".

[0175] As shown in spectrum 1502a (FIG. 15B) corresponding to 24.5% acetone vapour, the intensity of the acetone signature peak at about 791cm^"1 is about 7287 intensity counts, which is the "Sensor response" of the SERS based VOCs system. Spectrum 1502f is the control spectrum and the measurement standard deviation of the spectrum, 190 counts, is considered as the measurement SNR or baseline variation value.

[0176] The mass of the acetone molecules may be determined using Equation 6 described above. During SERS detection, the diameter of the laser spot is about 1 μηι. Also, the gap between the SERS substrate 1480 and the optical window of the gas chamber 1410 is about 0.6 mm. Therefore, as mentioned above, Equation 6 may be modified to Equation 7 and the total mass of acetone molecules may be determined as:

Total mass of acetone molecules = Density

= π(ΐ0^~6 )² (0.000 )m³ x 0.791g / cm³ = 1.49«g .

[0177] The saturation vapor pressure of acetone vapor at about 20°C is about 24.5% (186 mm/Hg). The effective mass of acetone molecules inside the laser spot may therefore be determined as (1.49 ng x 24.5% = 0.365 ng). Accordingly, the mass of acetone molecules within the excitation laser spot is estimated to be about 0.365 ng for about 24.5% acetone vapour.

[0178] From Equation 5,

Detection- Limit - e-365w— ^ ^ gOco nts = 9.5pg■

7287 counts

Therefore, the detection limit of acetone vapor measurement with the system 1400 is estimated to be about 9.5 pg.

[0179] The detection limit may also be calculated in the unit of ppm, using Equation 8 described above:

_T . . 245000 ppm _{1 ft}_

Detection - Limit = x l9ucounts

7287 counts

= 638% Appm .

[0180] For comparsion puiposes, measurements using acetone vapor (24.5%) have also been performed with a silver coated leaning nanopillars substrate using the set-up 1400 (FIG. 14). FIG. 16 shows the SERS spectra of the leaning nanopillar substrate (spectrum 1690) and the bimetallic nanogap substrate 1480 (spectrum 1692) for acetone vapor (24.5%) detection. The acetone signature peak (790cm^"1) is found in both spectra 1690, 1692. However, the peak intensity obtained with the bimetallic nano-gap structure substrate 1480 is about 28.7% higher than that obtained with the leaning nanopillars structure. The results reveal that the substrate 1480 with the bimetallic nanogap structure may provide sensitive VOCs detection.

[0181] As described above, the bimetallic nano-gap plasmonic structure substrate has been demonstrated for sensitive, reproducible and label free SERS based detection of VOCs (acetone vapor). Measurements using different concentrations of acetone vapor ranging from 0.7%, 1.5%, 3.5%, 10.3% and 24.5% have been performed. The measurement results are reproducible and the detection limit is found to be 9.5 pg (acetone molecules). The sensitivity of the bimetallic nanogap plasmonic structure substrate is found to be about 28.7% higher than that of the leaning silicon nanopillars substrate. With further system miniaturization, the technique may work as a portable, label free SERS based VOCs detection device for point-of-care applications in breath analysis, homeland security, chemical sensing and environmental monitoring. [0182] Various embodiments may also provide volatile organic compounds (VOCs) detection with surface enhanced Raman scattering (SERS) based on plasmonic bimetallic nano-gap substrate, which may be fabricated by deep UV photolithography. Measurements on ethanol (5.4%) and acetone (25.4%) vapours have been performed with a SERS VOCs sensing platform and highly reproducible results have been obtained. Such a system may find promising applications in health care, for example point-of-care VOCs measurement including on-site breath analysis for diabetes patients, homeland security, chemical sensing and environmental monitoring.

[0183] The fabrication of the bimetallic nanogap plasmonic nanostructure substrate may be as described above based on deep UV photolithography (DUV) at the wavelength of 250nm, followed by deep reactive ion etching and e-beam evaporation to deposit Ag (about 30 nm thick) and Au (about 15 nm thick) plasmonic active layers to form the bimetallic nanogap plasmonic nanostructure, which may be as shown in FIG. 2D.

[0184] Measurement set-up: FIG. 17 shows a schematic diagram of an optical sensing device 1700 of various embodiments. The optical sensing device 1700 may include a mechanical pump 1702 for injecting a carrier gas (e.g. air) into a bubbler chamber 1704 with a solution 1706, e.g. an ethanol solution, an acetone solution or a combination thereof, where at least one VOC vapour may be produced from. The VOC vapour produced may then be fed, for example through a tube 1708, into a gas or detection chamber 1710. As shown in FIG. 17, a sensor chip with the bimetallic nanogap plasmonic nanostructure substrate 1780 may be placed in the gas detection chamber 1710 for SERS detection. A window (e.g. atransparent optical window) 1712 may be provided through the chamber 1710, over the top of the substrate 1780 to allow the excitation and collection of SERS signal from the substrate 1780 through the window 1712. The VOC vapour may be removed from the chamber 1710 via the tube 1716 to a waste collector 1718.

[0185] SERS spectra may be recorded using a Raman microscope (Renishaw InVia) 1720 with a 633 nm excitation laser source 1722 or a 785 nm excitation laser source 1728. Light from the laser source 1722, 1728 may be coupled through a 50x objective lens 1714, which may also be used to collect the Raman signal generated. [0186] Acetone or ethanol vapour may be generated from the solution 1706 in the bubbler chamber 1704. During detection, excitation light from the He-Ne laser (633nm) 1722 may be incident on the Ag-Au coated nanostructures of the substrate 1780 through the objective lens (50 x, 0.75 N.A.) 1714 and the surface enhanced Raman spectrum may be recorded by the Raman spectrometer 1720. Different gas molecules possess characteristic fingerprint Raman peaks, which may help in the high sensitivity detection.

[0187] The different components or features of the sensing device 1700, including parameters, may be as described above in the context of the sensing device 300 (FIG. 3) and/or the sensing device 900 (FIG. 9).

[0188] Acetone vapour may be detected with the SERS VOCs sensing platform 1700. A reference spectrum (air) may be recorded before the acetone vapour injection into the chamber 1710, where the result may be similar to spectrum 700a (FIG.7), where no significant peak is found in the spectrum. After that, acetone vapour at about 25.4% may be generated and injected into the chamber 1710 and the surface enhanced Raman scattering signal excited at the bimetallic nanogap plasmonic nanostructure 1780 may be similar to spectrum 700b (FIG.7). A significant peak at about 790 cm^"1 spectral range may be observed, which is found to be correlated to the signature Raman peak of acetone molecule, as shown in FIG. 10B.

[0189] A cycling detection of acetone vapour may also be carried out, with the results obtained similar to spectra 700a, 700b, 700c, 700d (FIG. 7). After flushing the chamber 1710 with air to remove acetone vapour, a reference spectrum (air) may be recorded, where the result may be similar to spectrum 700c (FIG.7), where the 790 cm^"1 peak corresponding to acetone is not found in the Raman spectrum. When the same concentration of 25.4% acetone vapor is injected into the chamber 1710 to the surface of the sensing chip having the substrate 1780 again, the result obtained, which may be similar to spectrum 700d (FIG.7) shows the 790 cm^"1 peak. The cycling detection results reveal the high reproducibility of the SERS technique for VOCs detection.

[0190] The sensor platform has further been applied for ethanol vapour detection, with the results obtained similar to spectra 702a, 702b, 702c of FIG. 8. A reference spectrum (air) may be recorded before the injection of ethanol vapour into the chamber 1710, where the result may be similar to spectrum 702a. After that, ethanol vapor at about 5.4% may be generated and injected into the chamber 1710 to the surface of the bimetallic nanogap plasmonic nanostructure substrate 1780. The results obtained may be similar to spectrum 702b (FIG.8). A peak at about 880 cm^"1 spectral range may be observed, which is found to be correlated to the signature Raman peak of ethanol molecule, as shown in FIG. 10A. The surface of the sensor chip having the substrate 1780 may then be flushed with air for the removal of ethanol molecules. A reference spectrum (air) may be recorded, where the result may be similar to spectrum 702c (FIG. 8), where the 880 cm^"1 peak corresponding to ethanol is not found in the Raman spectrum after the air flushing process.

[0191] As described above, VOCs detection based on the surface enhanced Raman scattering signal excited at the bimetallic nanogap plasmonic structure has been demonstrated. Measurement results using ethanol (5.4%) and acetone (25.4%) vapor are highly reproducible and no chemical sensing layer is required. Such a system may find promising applications in health care, homeland security, chemical sensing and environmental monitoring.

[0192] While the invention has been particularly shown and described with reference to specific embodiments, it should be understood by those skilled in the art that various changes in form and detail may be made therein without departing from the spirit and scope of the invention as defined by the appended claims. The scope of the invention is thus indicated by the appended claims and all changes which come within the meaning and range of equivalency of the claims are therefore intended to be embraced.

Claims

1. A spectroscopic device for surface-enhanced Raman scattering (SERS), the spectroscopic device comprising:

a detection chamber comprising a window; and

a SERS-active substrate arranged in the detection chamber;

wherein the window is adapted to pass an excitation signal to illuminate the SERS-active substrate and further adapted to pass a SERS signal generated from the SERS-active substrate, and

wherein the SERS-active substrate is arranged spaced apart from an inner surface of the window facing the SERS-active substrate by a spacing of about 0.4 mm or less.

2. The spectroscopic device as claimed in claim 1, further comprising an objective lens configured to focus the excitation signal onto the SERS-active substrate to illuminate the SERS-active substrate and further configured to receive the SERS signal.

3. The spectroscopic device as claimed in claim 2, wherein the objective lens has a numerical aperture of about 0.75 or more.

4. The spectroscopic device as claimed in claim 2, wherein the objective lens has a magnification factor of 50 or more.

5. The spectroscopic device as claimed in claim 1, further comprising an excitation source configured to generate the excitation signal.

6. The spectroscopic device as claimed in claim 5, wherein the excitation source comprises a laser source.

7. The spectroscopic device as claimed in claim 6, wherein the excitation signal has a wavelength of about 633 nm.

8. The spectroscopic device as claimed in claim 1, wherein the excitation signal is dimensioned to illuminate a spot size of about 1 μιη on the SERS-active substrate.

9. The spectroscopic device as claimed in claim 1, further comprising a spectrometer configured to collect the SERS signal.

10. The spectroscopic device as claimed in claim 9, wherein the spectrometer comprises a diffraction grating for spectrally dispersing the SERS signal.

1 1. The spectroscopic device as claimed in claim 10, wherein the diffraction grating has a line density of about 1800 lines/mm.

12. The spectroscopic device as claimed in claim 10, wherein the diffraction grating has a spectral resolution of about 0.7 cm^"1.

13. The spectroscopic device as claimed in claim 1 , wherein the SERS-active substrate comprises a plurality of spaced-apart metallic nanostructures capable of generating hot-spots for generation of the SERS signal.

14. The spectroscopic device as claimed in claim 13, wherein each hot spot comprises an analyte molecule in direct contact with adjacent metallic nanostructures.

15. The spectroscopic device as claimed in claim 1, wherein the detection chamber is configured to receive one or more volatile organic compound vapours for interaction with the SERS-active substrate.

16. The spectroscopic device as claimed in claim 1, wherein the spectroscopic device is free of a cooling device.

17. A method of detecting surface-enhanced Raman scattering (SERS) signal, the method comprising: arranging a SERS-active substrate in a detection chamber, spaced apart from an inner surface of a window of the detection chamber facing the SERS-active substrate by a spacing of about 0.4 mm or less;

providing one or more volatile organic compounds to interact with the SERS- active substrate;

illuminating the SERS-active substrate with an excitation signal provided through the window; and

detecting a SERS signal passing through the window, the SERS signal being generated from the SERS-active substrate in response to the illumination by the excitation signal and the interaction with the one or more volatile organic compounds.

18. The method as claimed in claim 17, wherein the SERS-active substrate is maintained at room temperature.

19. The method as claimed in claim 17, wherein providing one or more volatile organic compounds comprises providing a plurality of volatile organic compounds to interact with the SERS-active substrate.

20. A method for multiplex detection of a plurality of volatile organic compounds using surface-enhanced Raman scattering (SERS), the method comprising:

providing a plurality of volatile organic compounds to interact with a SERS-active substrate;

illuminating the SERS-active substrate with an excitation signal;

detecting a SERS signal generated from the SERS-active substrate in response to the illumination by the excitation signal and the interaction with the plurality of volatile organic compounds; and

determining the identity of the plurality of volatile organic compounds from the detected SERS signal.