Highly Sensitive and Reliable Internal-Standard Surface-Enhanced Raman Scattering Microneedles for Determination of Bacterial Metabolites as Infection Biomarkers in Skin Interstitial Fluid

Abstract

Microneedles (MNs) are currently one of the most promising tools for skin interstitial fluid (ISF)-based biosensing, while it is still a challenge to expand the detectable biomarkers in ISF due to limited MNs types and detection techniques. Herein, highly sensitive internal-standard surface-enhanced Raman scattering microneedles (IS-SERS-MNs) were developed, which enabled the reliable detection of bacterial metabolites in ISF as new detectable biomarkers for infection diagnosis. The developed IS-SERS-MNs can not only directly detect pyocyanin (a representative bacterial metabolite) present in mouse dermal ISF but also indirectly detect pyocyanin in the hypodermis via its diffusion into the dermis, revealing a new possible pathway for the source of biomarkers in dermal ISF. Moreover, the SERS signal of pyocyanin was also clearly detected at real mouse wounds, indicating that the developed IS-SERS-MNs have great potential in minimally invasive and painless diagnosis of bacterial infection via a new ISF route. This work not only develops IS-SERS-MNs as a powerful tool for expanding the application of SERS-based MNs but also provides a new chance for ISF-related infection diagnosis.

Optical biosensing systems for a biological living body

“…SERS biosensors are effective tools for identifying and monitoring wound surface bacteria Mei et al. designed highly sensitive internal‐standard SERS microneedles for direct detection of bacterial metabolite in dermal interstitial fluid 205 . Perumal et al.…”

Revealing drug release and diffusion behavior in skin interstitial fluid by surface-enhanced Raman scattering microneedles

“…SERS D-MNs were prepared according to our previous work. 28 First, 100 mL of 0.01% HAuCl 4 was added to a round-bottom flask and boiled under stirring reflux. Then 1 mL of 1% sodium citrate was added and boiled for 30 min to prepare nearly 40 nm of spherical AuNPs.…”

“…SERS is an ultrasensitive vibrational spectroscopy technique showing great potential for in vivo detection. 25 A SERS-based MN sensing platform has proved to be a promising tool for the in situ fast detection of biological species in ISF such as glucose, 26 H + , 27 and bacterial metabolites, 28 which was improved for drug diffusion monitoring in this work. The experimental design is demonstrated in Fig.…”

Recent Progress of Surface-Enhanced Raman Spectroscopy for Bacteria Detection

“…SERS applied for bacteria detection has great advantages, such as a fast detection speed and high sensitivity without using labeling agents such as antibodies, and, in particular, it has simultaneous detection capabilities for multiple types of bacteria [ 35 , 36 ]. In addition, SERS is considered a promising tool to detect bacteria in infected wounds or blood tissue without damaging the actual sample structure [ 37 , 38 ].…”