Monitoring glucose levels is a key element of health surveillance. A research team has developed a battery-independent fluorescent nanosensor based on single-walled carbon nanotubes and an inactive form of the enzyme glucose oxidase (GOx). Since the enzyme is not in its active form, the analyte is not consumed during the measurement, allowing for continuous, reversible, and non-invasive bioimaging of glucose levels in bodily fluids and tissues, the team reports in the journal Angewandte Chemie.
Blood glucose levels are typically measured with GOx-based electrochemical sensors. However, these sensors produce toxic hydrogen peroxide as a by-product and also require bulky circuits and batteries, making it difficult to prepare implantable devices for continuous monitoring. In contrast, tiny SWCNTs can be integrated into tissues and provide bioimaging information: When excited by light, SWCNTs generate a near-infrared fluorescence signal that propagates through the tissue and can be easily recorded with non-invasive bioimaging techniques.
Unfortunately, manufacturing GOx-based SWCNT nanosensors is challenging, as the most effective technology for loading molecules onto SWCNTs—sonication—essentially deactivates the GOx molecules. Now, Markita P. Landry and her research team at the University of California in Berkeley, USA, have refuted the assumption that successful glucose measurement requires active GOx. Using ultrasound, they created GOx-loaded SWCNT sensors that reliably, selectively, and sensitively detected glucose, as demonstrated by glucose measurements in serum, plasma, and mouse brain slices.
The researchers attributed this surprising finding to the ability of the inactive GOx enzyme to bind to glucose without converting it. Binding alone was sufficient to modulate the fluorescence signal. To be entirely independent of GOx activity, the researchers also constructed a GOx enzyme lacking even the reactive group for glucose conversion. The resulting apo-GOx-SWCNT sensor recognized glucose in bodily fluids and mouse brain slices just as reliably as the original SWCNT-natural GOx conjugate.
The researchers point out that using inactive GOx molecules has major advantages. For example, the manufacturing process of GOx-SWCNT nanosensors can be simplified by using ultrasound as an effective preparation step. Additionally, since the analyte is not consumed by the enzyme reaction, no toxic by-products are produced, and the measurements are intrinsically reversible, allowing for non-invasive continuous glucose monitoring in tissue fluids.
Nishitani, S., et al. (2023). Conjugated glucose oxidase–carbon nanotube conjugates for tissue-translatable glucose nanosensors. Angewandte Chemie International Edition. doi.org/10.1002/ange.202311476.