title: Large-area surface-enhanced Raman spectroscopy imaging of brain ischemia by gold nanoparticles grown on random nanoarrays of transparent boehmite.
abstract: Although SERS spectroscopy, which is sensitive to molecular vibration states, offers label-free visualization of molecules, identification of molecules and their reliable large-area imaging remains to be developed. Limitation comes from difficulties in fabricating a SERS-active substrate with homogeneity over a large area. Here, we overcome this hurdle by utilizing a self-assembled nanostructure of boehmite that is easily achieved by a hydrothermal preparation of aluminum as a template for subsequent gold (Au) deposition. This approach brought about random arrays of Au-nanostructures with a diameter of ∼125 nm and a spacing of <10 nm, ideal for the hot-spots formation. The substrate, which we named "gold nanocoral" (GNC) after its coral reef-like shape, exhibited a small variability of signal intensities (coefficient value <11.2%) in detecting rhodamine 6G molecule when 121 spots were measured over an area of 10 × 10 mm(2), confirming high uniformity. The transparent nature of boehmite enabled us to conduct the measurement from the back-side of the substrate as efficiently as that from the front-side. We then conducted tissue imaging using the mouse ischemic brain adhered on the GNC substrate. Through nontargeted construction of two-dimensional-Raman-intensity map using differential bands from two metabolically distinct regions, that is, ischemic core and contralateral-control areas, we found that mapping using the adenine ring vibration band at 736 cm(-1) clearly demarcated ischemic core where high-energy adenine phosphonucleotides were degraded as judged by imaging mass spectrometry. Such a detection capability makes the GNC-based SERS technology especially promising for revealing acute energy derangement of tissues.
authors.affiliation: Frontier Core-Technology Laboratories, R & D Management Headquarters, FUJIFILM Corporation , 577, Ushijima, Kaisei-machi, Ashigarakami-gun, Kanagawa 258-8577, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Yamazoe
authors.forename: Masayuki
authors.initials: M
authors.lastname: Naya
authors.forename: Megumi
authors.initials: M
authors.lastname: Shiota
authors.forename: Takayuki
authors.initials: T
authors.lastname: Morikawa
authors.forename: Akiko
authors.initials: A
authors.lastname: Kubo
authors.forename: Takeharu
authors.initials: T
authors.lastname: Tani
authors.forename: Takako
authors.initials: T
authors.lastname: Hishiki
authors.forename: Tadashi
authors.initials: T
authors.lastname: Horiuchi
authors.forename: Makoto
authors.initials: M
authors.lastname: Suematsu
authors.forename: Mayumi
authors.initials: M
authors.lastname: Kajimura
mesh_terms: D000536:Aluminum Hydroxide / Q000737:chemistry*; D000537:Aluminum Oxide / Q000737:chemistry*; D000818:Animals; D001921:Brain / Q000473:pathology; D002545:Brain Ischemia / Q000473:pathology*; D003198:Computer Simulation; D006046:Gold / Q000737:chemistry*; D021621:Imaging, Three-Dimensional; D008297:Male; D013058:Mass Spectrometry; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D036103:Nanotechnology / Q000379:methods*; D012235:Rhodamines / Q000737:chemistry; D013059:Spectrum Analysis, Raman; D013379:Substrate Specificity; D013499:Surface Properties; D014732:Vibration
chemical_list: D012235:Rhodamines; C026188:rhodamine 6G; D000536:Aluminum Hydroxide; C069471:aluminum oxide hydroxide; D006046:Gold; D000537:Aluminum Oxide