Spectroelectrochemical Techniques’ Applications in Microfluidics: Comparison
View Latest Version
Please note this is a comparison between Version 2 by Dean Liu and Version 1 by Sagnik Basuray.

Spectroelectrochemical Techniques is attracting intensive interest for various research in analytical fields, ranging from biology to chemistry, material engineering, and others. 

  • spectroelectrochemistry
  • ultraviolet-visible SEC
  • surface-enhanced Raman spectroscopy SEC

1. Applications of SERS/Raman SEC in Microfluidics

One relatively straightforward but attractive configuration is proposed by Singh et al. for the highly sensitive detection of okadaic acid (OA) [168][1]. In this combined detection module, the microfluidic chip was employed to mix OA and the OA aptamer well. The phosphorene–gold nanocomposite-modified screen-printed carbon electrode (SPCE), which posed an affinity to the OA aptamer, was subsequently analyzed. The high performance of OA detection, whether qualitative or quantitative, demonstrated that the proposed point-of-care device can be deployed to perform on-farm assays in fishing units. 
“Immobile” SERS-active substrate means nanostructures with defined morphology (such as NPs, nanopillar forests, and nanodot arrays, among others) are permanently attached to substrates. For example, in the recent work published by Triroj et al., a diamond-like carbon thin film was prepared as a biosensing platform/substrate in the microfluidic device [169][2]. An in situ microfluidic analysis system is reported by Yuan et al. using nanostructured Au surfaces as the WE and simultaneously SERS-active substrate [93][3]. However, a drawback of “Immobile” SERS substrates is that they are intended for one-time use only [170][4]. With the pursuit of repeating “Immobile” SERS, Belder et al. successfully fulfilled the regeneration of the SERS substrate by applying pulsed voltages, which had been demonstrated with high reproducibility. This work incorporated the chemically roughened silver wire into the microfluidic chip and it was used for SERS measurements. The electrical regeneration process for the silver wire SERS substrate by applying a potential to clean the SERS substrate was achieved based on the proposed structure. Furthermore, the high reproducibility of Malachite green’s Raman spectra confirmed the achievement for the purpose of multiple recycling of the same SERS substrate.

2. Applications of UV-Vis SEC in Microfluidics

Similarly, the combined methodology of UV-Vis SEC and microfluidics has been widely used in biotechnology, catalysis, environmental protection, and others [7,171,172,173,174][5][6][7][8][9]. However, compared with the SERS/Raman SEC, the employment of UV-Vis SEC in microfluidics is more used, which is probably because the electrode substrate can be more easily prepared. In thisan interesting work reported by Colina et al., one easy method to employ or transfer commercial SWCNTs to different nonconductor and transparent supports as the WE is reported [174][9]. This work removes the often-employed hydraulic press step from the WE preparation process, significantly expanding the possibility of transferring the SWCNT film to almost any support. Another interesting point of this work is the employment of bidimensional SEC technology. Two different light beam arrangements, namely, normal and parallel transmission arrangements, are integrated into the same device to collect complementary information during the ferrocenemethanol electrode processes. Another interesting microfluidic device for UV-Vis SEC is proposed by Wang et al. [175][10]. A parallel transmission arrangement was adopted in this paper, which avoided the OTEs. Spectral measurements were made using an “in-house” constructed visible micro spectrometer which consisted of a deuterium/tungsten–halogen light source and a CCD spectrometer.
Seong et al. first reported one electrochemical point-of-care device with nanozymes for the high quantification of hydrogen peroxide (H2O2), a molecule for signaling within cells [172][7]. The electrodes (WE, CE, RE) were prepared using the market-available ITO electrodes. Then, the artificial nanostructured enzymes were immobilized in the microfluidics channel, showing a robust catalytic activity toward 3,3′,5,5′-tetramethylbenzidine (TMB) substrate in the presence of H2O2. The oxidized TMB with a blue color was subsequently analyzed using the UV-Vis SEC technique. Finally, based on the proposed device structure, a broad detection of H2O2 ranging from 1 µM to 3 mM and a low LOD of 1.62 µM were successfully obtained.

3. Summary & Outlook

Researchers have detailed the recent developments in composite SEC techniques, including UV-Vis SEC, Raman SEC, DFM SEC, NMR SEC, and recent progress in combining SEC techniques and microfluidics. In addition, a detailed analysis of the working principle and problems encountered in the selected applications are summarized. As mentioned above, the combination of electrochemistry and spectroscopy (SEC techniques) has been applied to diverse research fields ranging from the electron transfer process [55[11][12],176], reaction mechanisms [167][13], forensics sciences [177][14], and determination of intermediates and final products in electrochemical reactions [112,113][15][16]. Furthermore, the continuous advancement in nanotechnologies and the use of new materials (NPs [20[17][18],77], conductive polymers [11][19], and composite materials [17,178][20][21]) have further promoted SEC techniques. However, each of the SEC techniques mentioned above is still suffering some limitations, from the lab-scale to widespread practical use, as summarized below: UV-Vis SEC—For the UV-Vis SEC technique, OTEs are almost an inevitable topic in the normal transmission arrangement. (i) However, the frequently used OTEs such as ITO and FTO have the issue of fewer negative inert potential windows, and the thin film metallic OTEs are limited to electrochemical studies requiring high potentials due to the corresponding metal oxidation [50][22]. Therefore, considering the limitations of OTEs, more and more people are choosing parallel arrangement configurations. Compared with normal transmission arrangements, the parallel arrangement configuration is more favorable for conducting bidimensional SEC techniques [10][23]. (ii) However, in the parallel working mode, a perfect but difficult alignment of the light beams is required, complicating the operation process. SERS SEC—For the SERS SEC technique, according to the latest statistics from the website of the web of science, compared with other SEC technologies, the Raman SEC technique is the most widely used one. More and more combinations between SERS and electrochemistry have been used, considering the huge enhancement factor of the Raman signal [86][24]. Different metallic/composite NPs or other confined nanostructure morphologies such as nanopillar forests and nanodot arrays have been prepared and studied [101,102,103][25][26][27]. However, (i) the need for nanostructured SERS-active substrates will undoubtedly increase the experiment’s difficulty, cost, and time. (ii) An important issue is their reproducibility, considering the inherent batch-to-batch variances of NPs synthesis and the difficulty of storing. The other difficulties include (iii) background noise in the Raman signal and (iv) complicated instrumentation for the incorporation into a point-of-care or point-of-use system. Though handheld Raman spectroscopes exist, they are limited by their resolution and bandwidth. Hence, developing the Raman active SERS substrate will be a critical area of research for the broad application of this SERS SEC technique. NMR SEC—For the NMR SEC technique, this seems to be the most versatile as a secondary technique for identifying the molecular signature of the captured chemical moieties or the small biomolecules. However, due to the low sensitivity issue of the NMR technique, most of the uses for NMR SEC are focused on collecting information on a reaction intermediate during the electrochemical process to determine the possible reaction pathways [77,78,107][18][28][29]. The limitations to the widespread use of NMR SEC are: (i) the deterioration of magnetic field homogeneity due to metallic conducting electrodes; and (ii) using thin metallic or nonmetallic electrodes such as carbon microfibers or polymer electrodes usually requires complex fabrication protocols. Furthermore, nonmetallic electrodes usually have limited electrochemical applications due to the low achievable currents. DFM SEC—For the DFM SEC technique, unlike the other SEC techniques, this focuses more on the study between structural characteristics and catalyst activities from a single NP level. Since the understanding at the nanoscale level is critical to designing and producing stable and high-performance catalysts, however, by studying articles published in recent years, researchers can see that before the widespread applications in the research community, there is a considerable gap for this technology to cross. The reasons are listed here: (i) this technology has high requirements for the electrode materials: OTEs are required in DFM SEC. (ii) Tedious coupling procedures of the light and electric paths. (iii) Further, DFM SEC setups require extensive optics and might not be easy to be incorporated into a point-of-care or point-of-use system. (iv) The reliability and device-to-device variation in DFM SEC are also concerns.

References

  1. Young, E.W.; Beebe, D.J. Fundamentals of microfluidic cell culture in controlled microenvironments. Chem. Soc. Rev. 2010, 39, 1036–1048.
  2. Ramalingam, S.; Chand, R.; Singh, C.B.; Singh, A. Phosphorene-gold nanocomposite based microfluidic aptasensor for the detection of okadaic acid. Biosens. Bioelectron. 2019, 135, 14–21.
  3. Gao, F.; Kong, W.; He, G.; Guo, Y.; Liu, H.; Zhang, S.; Yang, B. SERS-active vertically aligned silver/tungsten oxide nanoflakes for ultrasensitive and reliable detection of thiram. Microchem. J. 2021, 165, 106046.
  4. Triroj, N.; Saensak, R.; Porntheeraphat, S.; Paosawatyanyong, B.; Amornkitbamrung, V. Diamond-like carbon thin film electrodes for microfluidic bioelectrochemical sensing platforms. Anal. Chem. 2020, 92, 3650–3657.
  5. Huang, Y.; Han, Y.; Gao, Y.; Gao, J.; Ji, H.; He, Q.; Tu, J.; Xu, G.; Zhang, Y.; Han, L. Electrochemical sensor array with nanoporous gold nanolayer and gold corona-nanocomposites enhancer integrated into microfluidic for simultaneous ultrasensitive lead ion detection. Electrochim. Acta 2021, 373, 137921.
  6. Nguyen, A.H.; Deutsch, J.M.; Xiao, L.; Schultz, Z.D. Online liquid chromatography–sheath-flow surface enhanced Raman detection of phosphorylated carbohydrates. Anal. Chem. 2018, 90, 11062–11069.
  7. Chikkaveeraiah, B.V.; Liu, H.; Mani, V.; Papadimitrakopoulos, F.; Rusling, J.F. A microfluidic electrochemical device for high sensitivity biosensing: Detection of nanomolar hydrogen peroxide. Electrochem. Commun. 2009, 11, 819–822.
  8. Ko, E.; Tran, V.-K.; Son, S.E.; Hur, W.; Choi, H.; Seong, G.H. Characterization of PtNP/GO nanozyme and its application to electrochemical microfluidic devices for quantification of hydrogen peroxide. Sens. Actuators B Chem. 2019, 294, 166–176.
  9. Kaaliveetil, S.; Yang, J.; Alssaidy, S.; Li, Z.; Cheng, Y.-H.; Menon, N.H.; Chande, C.; Basuray, S. Microfluidic Gas Sensors: Detection Principle and Applications. Micromachines 2022, 13, 1716.
  10. Garoz-Ruiz, J.; Heras, A.; Palmero, S.; Colina, A. Development of a novel bidimensional spectroelectrochemistry cell using transfer single-walled carbon nanotubes films as optically transparent electrodes. Anal. Chem. 2015, 87, 6233–6239.
  11. Itoh, T.; McCreery, R.L. In situ Raman spectroelectrochemistry of electron transfer between glassy carbon and a chemisorbed nitroazobenzene monolayer. J. Am. Chem. Soc. 2002, 124, 10894–10902.
  12. Wang, W.; Grace, H.M.; Flowers, P.A. Simple microfluidic device for spectroelectrochemistry. Microchem. J. 2022, 181, 107718.
  13. Anderson, B.A.; Krishnamurthy, R. Heterogeneous Pyrophosphate-Linked DNA–Oligonucleotides: Aversion to DNA but Affinity for RNA. Chem.—A Eur. J. 2018, 24, 6837–6842.
  14. Kaim, W.; Schwederski, B.; Dogan, A.; Fiedler, J.; Kuehl, C.J.; Stang, P.J. Metalla-supramolecular rectangles as electron reservoirs for multielectron reduction and oxidation. Inorg. Chem. 2002, 41, 4025–4028.
  15. Iwahara, J.; Clore, G.M. Detecting transient intermediates in macromolecular binding by paramagnetic NMR. Nature 2006, 440, 1227.
  16. Kavan, L.; Dunsch, L. Spectroelectrochemistry of carbon nanostructures. ChemPhysChem 2007, 8, 974–998.
  17. Koh, C.S.L.; Lee, H.K.; Phan-Quang, G.C.; Han, X.; Lee, M.R.; Yang, Z.; Ling, X.Y. SERS-and Electrochemically Active 3D Plasmonic Liquid Marbles for Molecular-Level Spectroelectrochemical Investigation of Microliter Reactions. Angew. Chem. 2017, 129, 8939–8943.
  18. Li, Z.; Li, W.; Jiang, Y.; Cai, H.; Gong, Y.; He, J. Raman characterization of the structural evolution in amorphous and partially nanocrystalline hydrogenated silicon thin films prepared by PECVD. J. Raman Spectrosc. 2011, 42, 415–421.
  19. Zhang, X.-P.; Jiang, W.-L.; Cao, S.-H.; Sun, H.-J.; You, X.-Q.; Cai, S.-H.; Wang, J.-L.; Zhao, C.-S.; Wang, X.; Chen, Z. NMR spectroelectrochemistry in studies of hydroquinone oxidation by polyaniline thin films. Electrochim. Acta 2018, 273, 300–306.
  20. Viehrig, M.; Rajendran, S.T.; Sanger, K.; Schmidt, M.S.; Alstrøm, T.S.; Rindzevicius, T.; Zór, K.; Boisen, A. Quantitative SERS assay on a single chip enabled by electrochemically assisted regeneration: A method for detection of melamine in milk. Anal. Chem. 2020, 92, 4317–4325.
  21. Premasiri, W.R.; Chen, Y.; Fore, J.; Brodeur, A.; Ziegler, L.D. SERS biomedical applications: Diagnostics, forensics, and metabolomics. In Frontiers and Advances in Molecular Spectroscopy; Elsevier: Amsterdam, The Netherlands, 2018; pp. 327–367.
  22. Benck, J.D.; Pinaud, B.A.; Gorlin, Y.; Jaramillo, T.F. Substrate selection for fundamental studies of electrocatalysts and photoelectrodes: Inert potential windows in acidic, neutral, and basic electrolyte. PLoS ONE 2014, 9, e107942.
  23. Garoz-Ruiz, J.; Heras, A.; Colina, A. Direct determination of ascorbic acid in a grapefruit: Paving the way for in vivo spectroelectrochemistry. Anal. Chem. 2017, 89, 1815–1822.
  24. Yuan, T.; Le Thi Ngoc, L.; van Nieuwkasteele, J.; Odijk, M.; van den Berg, A.; Permentier, H.; Bischoff, R.; Carlen, E.T. In situ surface-enhanced Raman spectroelectrochemical analysis system with a hemin modified nanostructured gold surface. Anal. Chem. 2015, 87, 2588–2592.
  25. Sinha, G.; Depero, L.E.; Alessandri, I. Recyclable SERS substrates based on Au-coated ZnO nanorods. ACS Appl. Mater. Interfaces 2011, 3, 2557–2563.
  26. Jeon, J.; Choi, N.; Chen, H.; Moon, J.-I.; Chen, L.; Choo, J. SERS-based droplet microfluidics for high-throughput gradient analysis. Lab A Chip 2019, 19, 674–681.
  27. Sun, D.; Cao, F.; Tian, Y.; Li, A.; Xu, W.; Chen, Q.; Shi, W.; Xu, S. Label-free detection of multiplexed metabolites at single-cell level via a SERS-microfluidic droplet platform. Anal. Chem. 2019, 91, 15484–15490.
  28. Fleischmann, M.; Hendra, P.J.; McQuillan, A.J. Raman spectra of pyridine adsorbed at a silver electrode. Chem. Phys. Lett. 1974, 26, 163–166.
  29. Patze, S.; Huebner, U.; Liebold, F.; Weber, K.; Cialla-May, D.; Popp, J. SERS as an analytical tool in environmental science: The detection of sulfamethoxazole in the nanomolar range by applying a microfluidic cartridge setup. Anal. Chim. Acta 2017, 949, 1–7.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)
ScholarVision Creations
Feedback