Gold nanodome-patterned microchips for intracellular surface-enhanced Raman spectroscopy

Abstract

While top-down substrates for surface-enhanced Raman spectroscopy (SERS) offer outstanding control and reproducibility of the gold nanopatterns and their related localized surface plasmon resonance, intracellular SERS experiments heavily rely on gold nanoparticles. These nanoparticles often result in varying and uncontrollable enhancement factors. Here we demonstrate the use of top-down gold-nanostructured microchips for intracellular sensing. We develop a tunable and reproducible fabrication scheme for these microchips. Furthermore we observe the intracellular uptake of these structures, and find no immediate influence on cell viability. Finally, we perform a proof-of-concept intracellular SERS experiment by the label-free detection of extraneous molecules. By bringing top-down SERS substrates to the intracellular world, we set an important step towards time-dependent and quantitative intracellular SERS.

Identification of Individual Exosome-Like Vesicles by Surface Enhanced Raman Spectroscopy

“…We consider the subtle difference discriminated by SERS in previous work on bulk EVs as a promising indication that detecting cancerous ELVs in complex mixtures would be possible with our single vesicle SERS approach. [28] It is of note that an alternative approach with the potential of single vesicle SERS was very recently developed by Lee et al. Their setup is based on Ag coated 'nanobowls' for hot-spot generation and SERS fingerprinting of EVs deposited into the nanobowls.…”

“…[25,26] In this respect, different types of SERS-substrates have been developed to obtain plasmon enhancement and record Raman spectra from (sub)cellular components down to the single biomolecule level. [27] These can be, but are not limited to, well defined nanostructured surfaces of gold [28] or silver [29] and (intracellular) aggregated Ag [30] or AuNP [31] . Both Ag-nanograin coated chips and precipitated AuNP clusters were recently applied for bulk EV measurements.…”

Ordered array of Ag semishells on different diameter monolayer polystyrene colloidal crystals: An ultrasensitive and reproducible SERS substrate

“…Lots of SERS substrates with “hot spots” have been prepared by different ways including chemical functional method9, electron lithography technique10 and self-assembled aggregation1112. Relatively speaking, as a simple, economic and effective way, nanosphere lithography (NSL) can be used to fabricate uniformly ordered nanoparticle arrays because of its good monodispersity, wide size range and realizable1314151617181920212223242526. For instance, by using NSL, Van Duyne’s group fabricated Au and Ag nanoparticle array on self-assembly monolayer polystyrene or silica nanospheres13141516.…”

“…fabricated Ag semishell arrays with controlled size and gaps by combining magnetron sputtering and reactive ion etching24. As SERS substrates, these ordered arrays have showed large area uniform Raman activity2526.…”

Nanodome coins for intracellular surface-enhanced Raman spectroscopy

“…2 shows a SEM image of such a gold-nanodome structured microcoin. More details on the fabrication and characterization of these chips will be presented in a later publication [13]. (Fig.…”