Sensitive SERS glucose sensing in biological media using alkyne functionalized boronic acid on planar substrates

• We present a novel glucose detection assay, which uses phenylboronic acid for molecular recognition, and SERS for signal transduction.
• We attached the alkyne moiety to phenylboronic acid for secondary binding, in order to enable indirect glucose detection.
• The alkyne bond exhibits a Raman peak at 1996 cm−1, which is free from spectral interference from most endogenous molecules.
• This assay demonstrates high selectivity for glucose over fructose and galactose, quantification, reusability, as well as clinical feasibility.

In this work, we propose a novel glucose binding mechanism on a highly sensitive SERS substrate, in order to overcome challenges in specific glucose detection in bio-fluids. We make use of phenylboronic acid as a receptor for saccharide capture onto the substrate and the ability of the captured glucose molecule to undergo secondary binding with an alkyne-functionalized boronic acid to form a glucose–alkyne–boronic acid complex. The formation of this complex shows high selectivity for glucose, over other saccharides. In addition, the alkyne group of the alkyne-functionalized boronic acid exhibits a distinct Raman peak at 1996 cm−1 in a biological silent region (1800–2800 cm−1) where most endogenous molecules, including glucose, show no Raman scattering, thus offering a high sensitivity over other SERS glucose sensing. The substrate offers long-term stability, as well as high SERS enhancement to the glucose–alkyne boronic acid complex on substrate. In addition, the reversibility of SERS signals at various incubation stages also shows reusability capabilities, whereas positive results in clinical urine samples demonstrate clinical feasibility. All these strongly suggest that this newly developed SERS-based assay offers great potential in glucose sensing.