In Situ Intracellular Spectroscopy with Surface Enhanced Raman Spectroscopy (SERS)-Enabled Nanopipettes

Abstract

We report on a new analytical approach to intracellular chemical sensing that utilizes a surface-enhanced Raman spectroscopy (SERS)-enabled nanopipette. The probe is comprised of a glass capillary with a 100-500 nm tip coated with gold nanoparticles. The fixed geometry of the gold nanoparticles allows us to overcome the limitations of the traditional approach for intracellular SERS using metal colloids. We demonstrate that the SERS-enabled nanopipettes can be used for in situ analysis of living cell function in real time. In addition, SERS functionality of these probes allows tracking of their localization in a cell. The developed probes can also be applied for highly sensitive chemical analysis of nanoliter volumes of chemicals in a variety of environmental and analytical applications.

Raman spectroscopy: techniques and applications in the life sciences

“…A more invasive but controlled approach involvde using AuNP coated microprobes for direct SERS measurement within the cell [332]. A similar idea was later carried out using a microprobe which had a more specific SERS label 'sandwich' for detecting low copy-number proteins, as illustrated in Figure 27(c) [333].…”

Laser-targeted photofabrication of gold nanoparticles inside cells

“…Without controlling the locations of particles, useful information is still gained, where particles uptaken by normal pathways in the cell can function as a type of nano-endoscope 3 , but there is significant interest in methods to control the uptake pathways and final destinations of nanoparticles in cells. Typical methods involve using conjugate tags with the particles, injecting the particles by micropipette, attaching particles to a nanopipette 5 or optimizing particle coatings to modulate typical cell-particle interaction pathways 6,7 . However, there are several limitations with these methods; bare nanoparticles do not readily penetrate cellular membranes, and even once inside the cell, they cannot move freely.…”

Scanning angle Raman spectroscopy: Investigation of Raman scatter enhancement techniques for chemical analysis

“…SERS nanopipettes have been used for in situ intracellular measurements of isolated intact HeLa human cervical carcinoma cells. 534 Gogotsi et al Carbon nanotubes have been commonly used for cellular probes, but not traditionally used for single cell SERS measurements. 535 Niu et al developed a carbon nanotube-tipped endoscope as an alternative substrate to avoid nanoparticle aggregation.…”