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Abstract
Signal enhancement of spectroscopies including terahertz time-domain spectroscopy (THz-TDS) and surface-enhanced Raman scattering (SERS) is a critical issue for effective molecular detection and identification. In this study, the sensing performance between THz-TDS and SERS individually accompanied by the proper plasmonic subwavelength structures was compared. For the precisely quantitative study on the optical properties of rhodamine 6G (R6G) dyes, SERS incorporates with the non-linearly enhanced Raman emissions at the molecular characteristic peaks while THz-TDS refers to the transmittance change and the shift of the spectral resonance. The local molecular density-dependent trade-off relationship between limit-of-detection and quenching was observed from both measurements. The specificity for two samples, R6G and methylene blue, is determined by the discriminations in spectral features such as the intensity ratio of assigned peaks in SERS and transmittance difference in THz-TDS. The comprehension of field enhancement by the specific nanostructures was supported by the finite-element method-based numerical computations. As a result, both spectroscopic techniques with the well-tailored nanostructures show great potential for highly sensitive, reproducible, label-free, and cost-effective diagnosis tools in the biomedical fields.
© 2020 Optical Society of America under the terms of the OSA Open Access Publishing Agreement
1. Introduction
Electromagnetic (EM) response from molecules inelastically interacted with incident photons involves information about intra-/inter- molecular motions, which is the most distinguishable part as compared to other specimens [1 –6]. Since a probability of inelastic scattering limits a signal-to-noise ratio (SNR) and sensitivity, however, many attempts have been devoted to enhance it. Surface plasmon resonance (SPR) property has been suggested to increase absorption cross-section of molecules by matching their corresponding characteristic frequency with a resonance frequency (fres) of an elaborate subwavelength structure of which size, shape, and distribution can be resonantly tuned [7 –10]. It allows that spectroscopies supported by the SPR become a promising candidate for contactless, sensitive, and label-free biomedical assay compared to other optical bio-chemical sensing techniques (e.g., optofluidics, fiber Bragg grating, and Förster resonance energy transfer) which have complex system designs, local environmental dependency, and low energy exchange efficiency issues. Among these, particularly, terahertz time-domain spectroscopy (THz-TDS) with low-photon energy and nonionizing radiation in broadband regime has been recently emerged, which is ideal to investigate accurate extended global intermolecular motions (i.e., vibrations and rotations), molecules themselves, and phonon vibrations in biosystems [6,11 –13].
For decades, there has been slow progress in the development of THz-TDS due to the lack of effective methods for the enhancement of molecular absorption at THz wave regime. Although the basic concepts of SPR have been attempted, the incident electric fields (E-fields) become unbound on the metallic surfaces which have the negatively infinite permittivity (i.e., perfect conductor) in THz regime. In order to overcome this issue, metamaterials, novel artificial designs with unusual EM properties, have been extensively studied owing to the technical advances in nanoscale fabrication in recent days [8,14 –18]. The tailored metamaterials within a subwavelength range (λ/10−λ/10000) demonstrate SPR-like behaviors with the specific fres which is adjustable by following the effective permittivity of surroundings as well as the geometry of active area [14 –16,19]. Especially, the nano slots produce the enhanced E-fields by a general factor of 2 while the magnetic (H) field remains almost constant [19]. Such an asymmetric |E/H| ratio near the slots provides the incredible benefits from the THz absorption of analytes, which makes the molecular identification available by the observation of transmittance difference (ΔT/T0) or frequency shift (Δf) even in very low concentration of biochemical compounds [20 –23]. Considering the concept of metamaterial cavity, the spatial confinement with the Purcell factor (Q/Veff) can be suggested to evaluate the device properties, where Q is the quality factor and Veff is the effective mode volume. Because the refractive index is involved into the Veff calculation, the Q/Veff ratio can be rather used to the refractive index sensing in cases with the split ring resonators and Fano resonators [24,25]. Still it is a big challenge to verify the validity of THz-TDS for universal uses and practical applications. Accordingly, comparison with THz-TDS and other powerful analytic tools such as surface-enhanced Raman scattering (SERS) is necessary.
SERS, its general enhancement factors (EFs) in a range of 104−106, has attracted great interest in identification of molecular fingerprint based on their rich vibrational frequencies [9,26 –28]. The fundamentals of such a phenomenon are a combination of EM enhancement and charge-transfer (CT) enhancement. The former originates from coherent oscillations of electron clouds of noble metallic nanostructures in proximity (i.e., hot spots) at which strong E-fields are confined, that is relevant to the localized SPR (LSPR) effect. The latter directly refers to an electron transition in the ground and excited states between metals and adsorbates, which is independent of the EM enhancement. Lately, the hybrid SERS designs improving CT enhancement have been utilized through the exploitation of dielectric substances (e.g., ZnO, SiO2, TiO2, etc) [29 –32]. Such a strategy accompanied by the metallic islands on dielectrics is associated with the dipole polarizability at the interface junctions, corresponding to the difference in energy levels.
In this work, we explored the potentials of THz-TDS for the practical, sensitive, and label-free small molecular diagnosis, by comparison with the SERS technique. The own standard platform for SERS and THz-TDS was prepared and their fundamental performance as sensing platform including the sensitivity (i.e., EF for SERS and ΔT/T0 for THz-TDS) and reliability was experimentally verified with rhodamine 6G (R6G) and, consequently, their quantitative analyses were examined and compared. For the R6G and methylene blue (MB), furthermore, the molecule-specificity of both techniques was investigated. In comparison with experimental results, their E-field distributions were also theoretically calculated based on a finite element method (FEM).
2. Experiments
2.1 Materials
Zinc nitrate hexahydrate (Zn(NO3)2·6H2O, 98%), gold(III) chloride trihydrate (HAuCl4, ≥ 99.9%), sodium borohydride (NaBH4, ≥ 96%), R6G (C28H31N2O3Cl, > 95%), and MB (C16H18ClN3S·xH2O) were purchased from Sigma-Aldrich Korea (Yongin, Korea). Hexamethylenetetramine (C6H12N4, > 98.5%) was prepared by Daejung Chemical & Metals (Siheung, Korea). All chemicals were used without any further purification. For characterization of SERS and THz platform, Raman probe materials (i.e., R6G and MB) dissolved and diluted (10−9−10−3 M) in de-ionized (DI) water were used. For THz-chips and SERS platform used in this work, detail information on their fabrication procedures is presented. (see Supplement 1, Fig. S1(a) and S1(b)).
2.2 Raman measurement
Raman spectra for probe molecules (i.e., R6G and MB) were measured via a Renishaw In Via Raman Microscope equipped with a He-Ne laser (λ∼ 633 nm). Laser of which power set to be 5.6 µW was exposed through a 50× objective lens (NA = 0.75). Raman scan was carried out with an acquisition time of 10 s three times to eliminate spike peaks. Raman spectra were recorded in a fingerprint range of 400−1800cm−1 with a spectral resolution of 0.4 cm−1, at 5 random points. For measurement, SERS platform was immersed in the dye solutions for 12 h and then dried using the N2 blow.
2.3 THz-TDS measurement
A conventional THz-TDS instrument for transmittance measurement was set up to estimate nano slot arrays. (see Supplement 1, Fig. S2 and S3). The measurement was performed under the N2 purged air environment to minimize a beam loss absorbed by water vapors. Transmittance spectra, derived from the 30-times averaged time-domain waveforms by the fast Fourier transform, were acquired from 3 chips mounted on a metal plate with an aperture size of 2×2 mm2 for individual molecular concentration. The transmittance (T(ω)) was calculated with the equation of $T(\omega )= {|{{E_{sample}}(\omega )/{E_{sub}}(\omega )} |^2}$, where Esample(ω) and Esub(ω) is the transmitted E-field through the nano slots with and without the analytes, respectively. Prior to assay, THz metamaterials were placed into the R6G and MB solutions for 12 h and then completely dried under the N2 flow.
2.4 Numerical simulations
The computations of E-field distributions in both SERS and THz-TDS were performed based on a FEM using an EM waves module in commercial COMSOL Multiphysics software. The geometric and optical parameters in simulations were summarized in details. (see Supplement 1, Table S1). Commonly, it was assumed that an active port boundary condition (BC) was at a top of air where EM wave was incident at a normal angle while a passive port BC at a bottom of substrate to pass light out of domain without reflection. Due to the structural complexity of gold nanoparticles-decorated zinc oxide nanorods on the flexible substrate (AuNPs/ZnONRs/F) and narrow hot spots (< 2 nm), a simplified two-dimensional (2D) model was constructed. For the periodic nano slots, a realistic three-dimensional (3D) design was applied.
3. Results and discussion
3.1 Structural and computational analysis of AuNPs/ZnONRs/F and nano slot metamaterial
The morphological properties and theoretically calculated E-field distributions of AuNPs/ZnONRs/F SERS platform and THz chips with the nano slots were investigated. For SERS, the AuNPs-decorated urchin-shaped compound structures were observed over the large areas without significant deformation and distortion as shown in Fig. 1(a) and 1(b). The optimal growth condition for the ZnONRs with a high aspect ratio was according to our previous researches [33,34]. Briefly, a diameter of ZnONRs is related to a diffusion rate of Zn2+ ions (i.e., solution concentration) while their length is proportional to a hydrothermal growth time. The wurtzite ZnONRs preferred to grow along the c-axis orientation normal to a surface, resulting in a high degree of anisotropicity [35]. It is noticed that the urchinically grown ZnONRs enabled the net density as well as the particle capture probability increased tremendously, which allowed themselves as the suitable SERS substances for the trace of small molecules. Under the ten successive ionic layer adsorption and reaction cycles, the AuNPs were densely and compactly decorated on the ZnONRs. Figure 1(c) shows the E-field profiles of AuNPs/ZnONRs/F under the exposure of λ = 633 nm calculated based on the FEM. The narrow hot spots between AuNPs contributed to the huge field enhancement (maxima∼ 1.43×106). For the THz chip, the aligned nano slots with the high length to width (l/w) ratio on the silicon (Si) substrate were observed without structural damages as shown in Figs. 1(d) and 1(e). The Si wafer with the high resistivity provided the benefits such as the constant refractive index in the measurement range (n Si≈ 3.41 in 0.2−2.0 THz) and its low absorption coefficient (α) for the maximum SNR. The incident THz beam could pass via the nano slots by the funneling effect but not for the Au layer of which thickness (150 nm) was larger than the skin depth (δ ∼ 90 and 70 nm at 0.76 and 1.30 THz, respectively). To achieve high resolution spectra below the first Rayleigh minima, the distance between each slot was maintained to be 40 and 10 µm along the transversal (x-axis) and longitudinal (y-axis) direction, respectively [21,36]. The active area with a size of 2×2 mm2 was designed to fully cover the beam size of incident THz wave (∼1 mm). From the computation, the polarization-dependent field profiles in local coverage of slot were observed. For the incident wave perpendicularly polarized (Ex-polarized) to the l of slot, as shown in Fig. 1(f), the intense E-fields (maxima∼ 102) were evaluated. In the contrary manner that they were aligned in parallel, the transmittance was sufficiently dropped down to be almost zero. (see Supplement 1, Fig. S4).
Fig. 1. Configuration and FEM-based numerical analysis of AuNPs/ZnONRs/F and nano slots metamaterial, (a,b) Morphological properties of the AuNPs-decorated urchin-like compound structures. (c) Computed 2D E-field distribution of the AuNPs/ZnONRs/F under the exposure at 633 nm. (d,e) Structural properties of the nano slots metamaterials with the high l/w ratio. (f) Calculated 3D E-field profile of the nano slots under the exposure at 0.76 THz.
3.2 SERS activities of the AuNPs/ZnONRs/F platform
Prior to the comparison between SERS and THz-TDS techniques, their chip performance (i.e., sensitivity and reliability) was investigated. For the SERS analysis, R6G, one of the representative Raman probe molecules, was used with its characteristic peaks at 1183 and 1648 cm−1. Figure 2(a) shows the sensitivity (i.e., EF) of AuNPs/ZnONRs/F SERS chip defined by a ratio for Raman intensity of SERS to non-SERS substrates. The EF can be expressed with the equation of [27]
Fig. 2. Raman activities of the AuNPs/ZnONRs/F SERS platform, (a) Raman spectra for the R6G molecules with different concentrations on the bare PET and AuNPs/ZnONRs/F platform. (b) Reproducibility and (c) SERS mapping images for the 1 mM R6G on AuNPs/ZnONRs/F platform.
3.3 Device performance of the THz chips with the nano slots
In order to determine the structural properties of nano slots for R6G detection, the optical features of the R6G pellet were preliminarily analyzed in the THz range. Figure 3(a) demonstrates the refractive index information calculated from the transmitted E-field via the R6G pellet (Epellet(ω)). The real part of refractive index (n(ω)) was described with
Fig. 3. Design of nano slots metamaterial-based THz chips, (a) Refractive index information of the R6G pellet in THz regime. (b) Device performance of the THz chips with the nano slots. Normalized transmittance spectra of (c) bare Si and (d) nano slots w/wo 1 µM R6G.
From the spectra, it was recommended that the architectures of nano slots should be designed to have the fres at 0.76 THz where the prominent peak of κ of R6G pellet was observed (i.e., resonance matching). The resonance quality of nano slot arrays is closely related to their structural information. The l assigns the fres with the equation of
where c0 is the speed of light while the w to the sensitivity. Therefore, the nano slots with the l = 80 µm, corresponded to the fres = 0.75 THz, were considered for R6G assay in the THz-TDS. For the nano slots with the l = 80 µm, as shown in Fig. 3(b), 30 chips without analytes were chosen to estimate the actual device characteristics. Their averaged fres and transmittance at the fres was measured to be 0.76 ± 0.01 THz and 0.49 ± 0.02, respectively, indicating the appropriate and stable device operation. In order to further investigate the resonance behavior, the change in transmittance was observed from the bare Si and nano slots with and without the 1 µM R6G as shown in Figs. 3(c) and 3(d). For the bare Si, there was no noticeable signal variation for R6G due to the absence of field enhancement. For the nano slots with the fres = 0.76 THz, on the other hand, the transmittance decreased by 10.78%, resulting from the strong absorption of THz wave by deposited R6G. Therefore, the metamaterial-based THz-TDS could be regarded as the potential alternative of existing spectroscopic techniques in biomedical applications in such low concentration.3.4 Comparison in a quantitative R6G assay between SERS and THz-TDS
For the direct comparison between two spectroscopic techniques, their effective detection range of R6G assay was examined. The effects of local molecular density on the limit-of-detection (LOD) and quenching were also explored. Herein, the R6G solutions used in this study were prepared by over 6 decades of dilution (1 mM−1 nM). Figure 4(a) presents the typical Raman peaks of R6G molecules observed at 611 (C-C-C in-plane vibration), 771 (C-H out-of-plane bend), 1183 (C-H in-plane bend), 1312 (N-H in-plane bend), 1361 (symmetric in-plane C-C stretching), 1510 (symmetric in-plane C-C stretching), and 1648 cm−1 (symmetric in-plane C-C stretching), respectively [30,31]. At the highest level of dilution, all Raman band was still clearly distinguishable from the fluorescent backgrounds. To precisely determine the LOD of AuNPs/ZnONRs/F SERS platform, its SNR was calculated using the formula of [37]
where S is the averaged Raman intensity and σi is the standard deviation of intensity at the specific peak. At 1648 cm−1, the SERS chip exhibited the reliable detection with the SNR of ∼ 4.8 for 1 nM R6G. Accordingly, its effective LOD could be decided to be ≤ 1 nM. Along the concentration, the Raman intensity at 1648 cm−1 was gradually decreased in the log-to-log scale with the linear fitting equation of log(y) = 6.30 + 0.45×log(x) and the correlation coefficient (R2) of 0.93 as shown in Fig. 4(b). From the result, the intensity variation behaved differently in two regions (1 nM−10 µM and 10 µM −1 mM) due to the quenching issue of R6G. The less slope in higher concentrations was of the relatively inefficient Raman emissions as well as the lowered quantum yields originated from the energy transfers between monomers and aggregates. It is well-known that the R6G dyes dissolved in DI water are likely to be aggregated under higher concentrations, typically ≥ 100 µM [38]. Thanks to the effective molecular adsorption by the complex nets, the R6G had more opportunity to be stacked together, resulting in the appearance of quenching in one order lower concentration (10 µM).Fig. 4. Direct comparison in quantitative analysis between SERS and THz-TDS, (a) Raman spectra and (b) Raman intensity variations at 1648 cm−1 along the R6G concentrations on the AuNPs/ZnONRs/F SERS platform. (c) Normalized transmittance spectra and (d) transmittance differences at 0.76 THz for the different concentrations of R6G on the nano slots with the fres = 0.76 THz.
Meanwhile, the variations of transmittance spectra were used as the criterion for the quantitative R6G assay in the THz-TDS. The measured spectra for the R6G on nano slots normalized respect to the bare chips as demonstrated in Fig. 4(c). For the THz-TDS, herein, the Δf was explained by the quantity of substances as well as the effective permittivity in active areas [23,39,40]. It is expressed by the following relationship of
Table 1. Comparison of sensing performance for R6G between SERS and THz-TDS techniques.
3.5 Molecular-specific diagnosis in SERS and THz-TDS
In order to explore the feasibility for molecule-specific SERS and THz-TDS, MB, another Raman probe material, was employed. Figure 5(a) shows the prominent Raman peaks of MB at 445, 501, 770, 1154, 1301, 1394, and 1623 cm−1 observed from the 1 mM MB on the SERS chip, which were in good agreement with previous literatures [41,42]. The bands at 445 and 501 cm−1 corresponded to the C-N-C skeletal deformation, while 770 and 1154 cm−1 to the C-H in-plane bending, 1301 cm−1 to the C-H in-plane ring deformation, 1394 cm−1 to the C-N symmetrical stretching, and 1623 cm−1 to the C-C ring stretching, respectively. The AuNPs/ZnONRs/F platform exhibited the superior capability for the quantitative MB detection as shown in inset of Fig. 5(a). In general, the Raman bands are associated with molecular vibrational modes of which coordinates are a combination of changes in atomic positions. As seen in the difference in molecular structures between R6G (Fig. 4(a)) and MB (Fig. 5(a)), these particles demonstrated the inherent Raman spectral features and were simultaneously differentiated by the intensity ratio at the certain peaks, which was requisite for the label-free diagnosis (Fig. 5(b)). The dominant peaks (color-labeled) were observed at 611, 1362, and 1648 cm−1 for the R6G while the peaks at 445, 1394, and 1623 cm−1 for the MB. Therefore, the versatile AuNPs/ZnONRs/F sensors with excellent sensitivity, reproducibility, and specificity are potentially desirable for the practical biomedical assay based on the SERS. Prior to the MB analysis in the THz-TDS, its α feature was explored in the THz range as shown in inset of Fig. 5(c). In particular, there are three hydrate types of MB; anhydrate, dihydrate, and pentahydrate [43]. The anhydrous basis MB, without crystalline water, used in this study exhibited no prominent absorption peaks in 0.2−2.0 THz. Therefore, another THz chip was considered with the fres = 1.30 THz at which the gap in α between R6G and MB was the largest and consequently the corresponding l of nano slots was settled to be 44.5 µm. For spectroscopies, in general, their sensitivities are related to the characteristic absorption features corresponding to the vibrational/rotational states. Under the resonance matching condition, they can be further enhanced, although it is not exactly proportional to the molecular optical properties and field enhancement due to the non-ideal factors including the Q factor of system, film uniformity during the drying, and field/molecular distribution profiles in the active region [21]. This phenomenon is also observed with the R6G and MB in the THz regime. At 0.76 THz, the weak absorption peak of R6G (Fig. 3(a) and inset of Fig. 5(c)) was observed while no characteristic features for the MB (inset of Fig. 5(c)). Despite of lower α value of R6G, compared with the MB, its transmittance difference was more dominantly changed due to the enhanced molecular THz absorption. Meanwhile, just a few-percentage signal change discriminated MB activity explicitly originated from its α value only due to no resonance matching. Figure 5(d) shows that such a phenomenon also attributed to the R6G and MB on the nano slots with the fres = 1.30 THz. At 1 mM, the transmittance difference of MB (0.76 THz), R6G (1.30 THz), and MB (1.30 THz) was extracted to be 7.4, 9.4, and 14.4%, respectively, which was well-consistent with their α spectra. From the results, the fingerprints (or library) of R6G and MB would be established by the combination of absence/presence of resonance coupling and parametric investigation. In this respect, it is remarkable that the THz-TDS successfully specified the R6G and MB, famous Raman probes, based on their optical features in the THz regime.
Fig. 5. Comparison in molecular identification between SERS and THz-TDS, (a) Raman spectrum for the 1 mM MB and (b) selectivity for R6G and MB on the AuNPs/ZnONRs/F SERS platform. Molecular-identification using the nano slots with the fres= (c) 0.76 and (d) 1.30 THz. The inset of (a) shows the Raman intensity variations of MB at 445 cm−1 along the concentrations. The inset of (c) demonstrates the absorption coefficient of R6G and MB in THz regime.
4. Conclusions
We investigated and compared the analytic activities of AuNPs/ZnONRs/F SERS platform and THz spectroscopy with the nano slots based sensing chips for the trace of small molecules. The outstanding feasibilities for quantitative and reproducible SERS came from the uniformity of AuNPs over the entire platform. The sensitivity, R2, and effective LOD of SERS was determined to be 8.98×105, 0.93, and ≤ 1 nM, respectively. The relatively inefficient Raman emissions arose from the 1 mM−10 µM R6G at which the molecular quenching occurred. The R6G and MB were identified by their fingerprint spectra responsible for the vibrational modes involving the information about molecular bonding and symmetry. Meanwhile, the nano slots with the high l/w ratio demonstrated the attractive metamaterial properties including the tunable fres, polarization-dependency, R2 of 0.92, and LOD of 10 nM. The enhancement of THz-molecule interactions was related to the resonance matching with the fres of nano slots. Owing to the low local molecular density in the active areas, the THz-TDS analysis became independent of the quenching effect. For the separation of R6G and MB, their transmittance difference based on the α was analyzed by utilizing two types of nano slots with the fres = 0.76 and 1.30 THz. Although there were no characteristic absorption features of the specimens in the THz regime, the THz-TDS effectively distinguished them based on their α properties. Therefore, these results demonstrated that the THz-TDS functionalized analytic tool accompanied by the advanced metamaterials could be compatible with the SERS for the trace of biospecimens in the practical applications.
Funding
Korea Institute of Science and Technology (2E30520); National Research Foundation of Korea (CAMM-2019M3A6B3030638, NRF-2020R1A2C2007077).
Acknowledgements
We acknowledge Dr. Sang-Soo Lee (KIST) for the support of Raman facility (Renishaw).
Disclosures
The authors declare no conflicts of interest.
See Supplement 1 for supporting content.
References
1. J. Kern, R. Alonso-Mori, R. Tran, J. Hattne, R. J. Gildea, N. Echols, C. Glöckner, J. Hellmich, H. Laksmono, R. G. Sierra, B. Lassalle-Kaiser, S. Koroidov, A. Lampe, G. Han, S. Gul, D. DiFiore, D. Milathianaki, A. R. Fry, A. Miahnahri, D. W. Schafer, M. Messerschmidt, M. M. Seibert, J. E. Koglin, D. Sokaras, T.-C. Weng, J. Sellberg, M. J. Latimer, R. W. Grosse-Kunstleve, P. H. Zwart, W. E. White, P. Glatzel, P. D. Adams, M. J. Bogan, G. J. Williams, S. Boutet, J. Messinger, A. Zouni, N. K. Sauter, V. K. Yachandra, U. Bergmann, and J. Yano, “Simultaneous femtosecond X-ray spectroscopy and diffraction of photosystem II at room temperature,” Science 340(6131), 491–495 (2013). [CrossRef]
2. K. M. Lange, A. Kothe, and E. F. Aziz, “Chemistry in solution: recent techniques and applications using soft X-ray spectroscopy,” Phys. Chem. Chem. Phys. 14(16), 5331–5338 (2012). [CrossRef]
3. I. Amenabar, S. Poly, M. Goikoetxea, W. Nuansing, P. Lasch, and R. Hillenbrand, “Hyperspectral infrared nanoimaging of organic samples based on Fourier transform infrared nanospectroscopy,” Nat. Commun. 8(1), 14402 (2017). [CrossRef]
4. I. Maeng, S. Lim, S. J. Chae, Y. H. Lee, H. Choi, and J. H. Son, “Gate-controlled nonlinear conductivity of Dirac fermion in graphene field-effect transistors measured by terahertz time-domain spectroscopy,” Nano Lett. 12(2), 551–555 (2012). [CrossRef]
5. H. Hu, X. Yang, F. Zhai, D. Hu, R. Liu, K. Liu, Z. Sun, and Q. Dai, “Far-field nanoscale infrared spectroscopy of vibrational fingerprints of molecules with graphene plasmons,” Nat. Commun. 7(1), 12334 (2016). [CrossRef]
6. D. Patterson, M. Schnell, and J. M. Doyle, “Enantiomer-specific detection of chiral molecules via microwave spectroscopy,” Nature 497(7450), 475–477 (2013). [CrossRef]
7. J. Zhou, Q. Qi, C. Wang, Y. Qian, G. Liu, Y. Wang, and L. Fu, “Surface plasmon resonance (SPR) biosensors for food allergen detection in food matrices,” Biosens. Bioelectron. 142, 111449 (2019). [CrossRef]
8. S. Sugumaran, M. F. Jamlos, M. N. Ahmad, C. S. Bellan, and D. Schreurs, “Nanostructured materials with plasmonic nanobiosensors for early cancer detection: A past and future prospect,” Biosens. Bioelectron. 100, 361–373 (2018). [CrossRef]
9. D.-K. Lim, K.-S. Jeon, J.-H. Hwang, H. Kim, S. Kwon, Y. D. Suh, and J.-M. Nam, “Highly uniform and reproducible surface-enhanced Raman scattering from DNA-tailorable nanoparticles with 1-nm interior gap,” Nat. Nanotechnol. 6(7), 452–460 (2011). [CrossRef]
10. M. Autore, P. Li, I. Dolado, F. J. Alfaro-Mozaz, R. Esteban, A. Atxabal, F. Casanova, L. E. Hueso, P. Alonso-González, J. Aizpurua, A. Y. Nikitin, S. Vélez, and R. Hillenbrand, “Boron nitride nanoresonators for phonon-enhanced molecular vibrational spectroscopy at the strong coupling limit,” Light: Sci. Appl. 7(4), 17172 (2018). [CrossRef]
11. M. T. Ruggiero, J. Sibik, R. Orlando, J. A. Zeitler, and T. M. Korter, “Measuring the elasticity of poly-L-proline helices with terahertz spectroscopy,” Angew. Chem., Int. Ed. 55(24), 6877–6881 (2016). [CrossRef]
12. D. A. Turton, H. M. Senn, T. Harwood, A. J. Lapthorn, E. M. Ellis, and K. Wynne, “Terahertz underdamped vibrational motion governs protein-ligand binding in solution,” Nat. Commun. 5(1), 3999 (2014). [CrossRef]
13. D. F. Plusquellic, K. Siegrist, E. J. Heilweil, and O. Esenturk, “Applications of terahertz spectroscopy in biosystems,” ChemPhysChem 8(17), 2412–2431 (2007). [CrossRef]
14. A. Salim and S. Lim, “Recent advances in the metamaterial-inspired biosensors,” Biosens. Bioelectron. 117, 398–402 (2018). [CrossRef]
15. B. Ng, J. Wu, S. M. Hanham, A. I. Fernández-Domínguez, N. Klein, Y. F. Liew, M. B. H. Breese, M. Hong, and S. A. Maier, “Spoof plasmon surfaces: a novel platform for THz sensing,” Adv. Opt. Mater. 1(8), 543–548 (2013). [CrossRef]
16. Z. Han, Y. Zhang, and S. I. Bozhevolnyi, “Spoof surface plasmon-based stripe antennas with extreme field enhancement in the terahertz regime,” Opt. Lett. 40(11), 2533–2536 (2015). [CrossRef]
17. C. R. Williams, S. R. Andrews, S. A. Maier, A. I. Fernández-Domínguez, L. Martín-Moreno, and F. J. García-Vidal, “Highly confined guiding of terahertz surface plasmon polaritons on structured metal surfaces,” Nat. Photonics 2(3), 175–179 (2008). [CrossRef]
18. Y. Zhang and Z. Han, “Spoof surface plasmon based planar antennas for the realization of terahertz hotspots,” Sci. Rep. 5(1), 18606 (2016). [CrossRef]
19. M. A. Seo, H. R. Park, S. M. Koo, D. J. Park, J. H. Kang, O. K. Suwal, S. S. Choi, P. C. M. Planken, G. S. Park, N. K. Park, Q. H. Park, and D. S. Kim, “Terahertz field enhancement by a metallic nano slit operating beyond the skin-depth limit,” Nat. Photonics 3(3), 152–156 (2009). [CrossRef]
20. H. R. Park, K. J. Ahn, S. Han, Y. M. Bahk, N. Park, and D. S. Kim, “Colossal absorption of molecules inside single terahertz nanoantennas,” Nano Lett. 13(4), 1782–1786 (2013). [CrossRef]
21. S. H. Lee, D. Lee, M. H. Choi, J. H. Son, and M. Seo, “Highly sensitive and selective detection of steroid hormones using terahertz molecule-specific sensors,” Anal. Chem. 91(10), acs.analchem.9b01066 (2019). [CrossRef]
22. W. Xu, L. Xie, J. Zhu, X. Xu, Z. Ye, C. Wang, Y. Ma, and Y. Ying, “Gold nanoparticle-based terahertz metamaterial sensors: mechanisms and applications,” ACS Photonics 3(12), 2308–2314 (2016). [CrossRef]
23. S. J. Park, J. T. Hong, S. J. Choi, H. S. Kim, W. K. Park, S. T. Han, J. Y. Park, S. Lee, D. S. Kim, and Y. H. Ahn, “Detection of microorganisms using terahertz metamaterials,” Sci. Rep. 4(1), 4988 (2015). [CrossRef]
24. M. Gupta and R. Singh, “Terahertz sensing with optimized Q/Veff metasurface cavities,” Adv. Opt. Mater. 8(16), 1902025 (2020). [CrossRef]
25. Y. K. Srivastava, R. T. Ako, M. Gupta, M. Bhaskaran, S. Sriram, and R. Singh, “Terahertz sensing of 7 nm dielectric film with bound states in the continuum metasurfaces,” Appl. Phys. Lett. 115(15), 151105 (2019). [CrossRef]
26. V. V. Thacker, L. O. Herrmann, D. O. Sigle, T. Zhang, T. Liedl, J. J. Baumberg, and U. F. Keyser, “DNA origami based assembly of gold nanoparticle dimers for surface-enhanced Raman scattering,” Nat. Commun. 5(1), 3448 (2014). [CrossRef]
27. D. G. Montjoy, J. H. Bahng, A. Eskafi, H. Hou, and N. A. Kotov, “Omnidispersible hedgehog particles with multilayer coatings for multiplexed biosensing,” J. Am. Chem. Soc. 140(25), 7835–7845 (2018). [CrossRef]
28. Q. Zhang, N. Large, and H. Wang, “Gold nanoparticles with tipped surface structures as substrates for single-particle surface-enhanced Raman spectroscopy: concave nanocubes, nanotrisoctahedra, and nanostars,” ACS Appl. Mater. Interfaces 6(19), 17255–17267 (2014). [CrossRef]
29. I. Alessandri and J. R. Lombardi, “Enhanced Raman scattering with dielectrics,” Chem. Rev. 116(24), 14921–14981 (2016). [CrossRef]
30. H. Tang, G. Meng, Q. Huang, Z. Zhang, Z. Huang, and C. Zhu, “Arrays of cone-shaped ZnO nanorods decorated with Ag nanoparticles as 3D surface-enhanced Raman scattering substrates for rapid detection of trace polychlorinated biphenyls,” Adv. Funct. Mater. 22(1), 218–224 (2012). [CrossRef]
31. C. C. Chang, K. H. Yang, Y. C. Liu, T. C. Hsu, and F. Mai, “Surface-enhanced Raman scattering-active Au/SiO2 nanocomposites prepared using sonoelectrochemical pulse deposition methods,” ACS Appl. Mater. Interfaces 4(9), 4700–4707 (2012). [CrossRef]
32. H. Fang, C. X. Zhang, L. Liu, Y. M. Zhao, and H. J. Xu, “Recyclable three-dimensional Ag nanoparticle-decorated TiO2 nanorod arrays for surface-enhanced Raman scattering,” Biosens. Bioelectron. 64, 434–441 (2015). [CrossRef]
33. W. Kim, S. H. Lee, S. H. Kim, J. C. Lee, S. W. Moon, J. S. Yu, and S. Choi, “Highly reproducible Au-decorated ZnO nanorod array on a graphite sensor for classification of human aqueous humors,” ACS Appl. Mater. Interfaces 9(7), 5891–5899 (2017). [CrossRef]
34. S. H. Lee, S. H. Kim, and J. S. Yu, “Metal-semiconductor-metal near-ultraviolet (∼380 nm) photodetectors by selective area growth of ZnO nanorods and SiO2 passivation,” Nanoscale Res. Lett. 11(1), 333 (2016). [CrossRef]
35. S. Baruah and J. Dutta, “Hydrothermal growth of ZnO nanostructures,” Sci. Technol. Adv. Mater. 10(1), 013001 (2009). [CrossRef]
36. J. W. Lee, M. A. Seo, D. H. Kang, K. S. Khim, S. C. Jeoung, and D. S. Kim, “Terahertz electromagnetic wave transmission through random arrays of single rectangular holes and slits in thin metallic sheets,” Phys. Rev. Lett. 99(13), 137401 (2007). [CrossRef]
37. R. L. McCreery, Raman spectroscopy for chemical analysis, Wiley, Hoboken, NJ, USA, 2000.
38. R. Vogel, M. Harvey, G. Edwards, P. Meredith, N. Heckenberg, M. Trau, and H. Rubinsztein-Dunlop, “Dimer-to-monomer transformation of rhodamine 6G in aqueous PEO-PPO-PEO block copolymer solutions,” Macromolecules 35(6), 2063–2070 (2002). [CrossRef]
39. S. J. Park, J. T. Hong, S. J. Choi, H. S. Kim, W. K. Park, S. T. Han, J. Y. Park, S. Lee, D. S. Kim, and Y. H. Ahn, “Detection of microorganisms using terahertz metamaterials,” Sci. Rep. 4(1), 4988 (2015). [CrossRef]
40. S. J. Park, B. H. Son, S. J. Choi, H. S. Kim, and Y. H. Ahn, “Sensitive detection of yeast using terahertz slot antennas,” Opt. Express 22(25), 30467–30472 (2014). [CrossRef]
41. M. Hou, Y. Huang, L. Ma, and Z. Zhang, “Compositional analysis of ternary and binary chemical mixtures by surface-enhanced Raman scattering at trace levels,” Nanoscale Res. Lett. 10(1), 437 (2015). [CrossRef]
42. K. Wong-Ek, P. Eiamchai, M. Horprathum, V. Patthanasettakul, P. Limnonthakul, P. Chindaudom, and N. Nuntawong, “Silver nanoparticles deposited on anodic aluminum oxide template using magnetron sputtering for surface-enhanced Raman scattering substrate,” Thin Solid Films 518(23), 7128–7132 (2010). [CrossRef]
43. S. Yan, H. Zhang, Z. Yang, M. Tang, M. Zhang, C. Du, H. L. Cui, and D. Wei, “Transformation and dehydration kinetics of methylene blue hydrates detected by terahertz time-domain spectroscopy,” RSC Adv. 7(66), 41667–41674 (2017). [CrossRef]
