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Bai S, Ren XL, Obata K, Ito Y, Sugioka K. Label-free trace detection of bio-molecules by liquid-interface assisted surface-enhanced Raman scattering using a microfluidic chip. Opto-Electron Adv 5, 210121 (2022). doi: 10.29026/oea.2022.210121
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Label-free trace detection of bio-molecules by liquid-interface assisted surface-enhanced Raman scattering using a microfluidic chip
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Abstract
Surface-enhanced Raman scattering (SERS), owing to its high sensitivity based on localized surface plasmon resonance of nanostructured metals, is recently attracting much attention to be used for biotechnology, such as cell imaging and tumor therapy. On the other hand, the trace detection of bio-molecules with large molecular weight is still challenging because the troublesome treatment of SERS substrate using coupling or cross-linking agents is required. In this paper, we apply liquid interface assisted SERS (LI-SERS) method, which provides unique features of collection and self-immobilization of analyte molecules on the SERS substrate, to realize the label-free trace detection of bio-molecules with detection limits of pM ~ fM. Specifically, deoxyribonucleic acid (DNA) discrimination and quantitative detection of β-Amyloid (Aβ) in trace-concentration are demonstrated to illustrate the ultrahigh sensitivity and versatility of the LI-SERS method. The results suggest LI-SERS is promising for the early-stage diagnosis of diseases such as virus infection and Alzheimer's disease.-
Keywords:
- femtosecond laser processing /
- LI-SERS /
- microfluidic chip /
- DNA /
- β-Amyloid
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References
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Supplementary information for Label-free trace detection of bio-molecules by liquid-interface assisted surface-enhanced Raman scattering using a microfluidic chip 
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Bai S, Ren XL, Obata K, Ito Y, Sugioka K. Label-free trace detection of bio-molecules by liquid-interface assisted surface-enhanced Raman scattering using a microfluidic chip. Opto-Electron Adv 5, 210121 (2022). doi: 10.29026/oea.2022.210121
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Figure 1.
Schematic of laser fabrication system for microfluidic SERS chips. For generation of a second harmonic of 515 nm wavelength from 1030 nm and 233 fs laser, LBO was used. A half-wave plate and a polarizing beamsplitter cube are used to control laser energy. 3D precision motorized stage and an automatic shutter are controlled by the PC.
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Figure 2.
(a) Schematic of the fabrication procedure for the microfluidic SERS chip using hybrid fs laser processing. (1. Glass microfluidic chip fabricated by fs laser assisted chemical etching. 2. Femtosecond laser selective ablation at the bottom surface of the microchannel. 3. Selective metallization on the laser ablated region by electroless metal plating. 4. Nanostructuring on the metal film by fs LIPSS.) (b) Photograph of microfluidic SERS chip fabricated by hybrid fs laser processing. (c) Optical microscope image showing the SERS substrate formed at the bottom surface of the microchannel embedded in the glass substrate. SEM images of (d) original metal film, (e) ripples generated by 1st laser scanning and (f) nanodots generated by 2nd laser scanning (Insert: low magnification of SEM image). (g) Raman spectra of 10-9 M Rhodamine 6G (R6G) on 2-D (black) and 1-D (red) nanostructured SERS substrates.
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Figure 3.
(a, c) Schematics for regular SERS and LI-SERS measurements of analyte solutions in the microchannel, respectively. (b, d) Raman spectra of DNA bases, adenine (A) and cytosine, (C) and thymine (T), measured using microfluidic SERS chips with 2-D nanostructured SERS substrates by regular SERS for 1 μM concentration and LI-SERS for 1 fM concentration, respectively.
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Figure 4.
(a) Simulation of the fluid temperature and the pressure distributions in the liquid on the SERS substrate near the liquid-interface induced by laser heating. (b) The diagram of local aggregation of analyte molecules governed by Marangoni flow and optical trapping. (c) Immobilized R6G molecules on substrate by LI-SERS measurements.
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Figure 5.
(a) Raman spectra for DNA sequences at different concentrations measured by the LI-SERS method. (b) Raman spectra for two DNA sequences (10 fM) consisting of different ratios of bases. The C=O stretching at 1640 cm–1 and the C=N stretching at 1474 cm–1 are highlighted with gray bars. (c) Raman spectra of Aβ (29-40) at different concentrations as measured by the LI-SERS method. (d) Variation of Raman intensity, which is averages from ten measurements at each concentration at 1271 cm–1 with the error less than ~10% as a function of concentration. The red line is the linear fitting of Aβ (29–40) concentrations and Raman intensity at 1271 cm–1.
