High vanillic acid (HVA) is the main metabolite of the central nervous system neurotransmitter dopamine. Unlike dopamine, it can cross the blood-brain barrier and enter the circulatory system. Therefore, the fluctuation of HVA in the blood is closely related to the activity of dopamine in the central nervous system (CNS). In clinical practice, dopamine testing requires complex implantable analysis of cerebrospinal fluid through neurosurgical procedures, which can easily lead to infection and permanent functional damage.In contrast, blood samples are easy to collect and have less invasiveness during implantation. Therefore, the dynamic study of blood HVA provides a powerful supplement for studying dopamine activity. In addition, HVA in the blood is also used as an indicator to evaluate the progression of schizophrenia and the effectiveness of related therapeutic drugs. It is also related to the pathogenesis of neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease. Therefore, real-time monitoring of HVA in the blood is of great significance for studying central dopamine activity, disease pathogenesis, and evaluating drug efficacy.

However, real-time monitoring of HVA in the body has not yet been achieved. The main challenge is the presence of a large amount of active substances in the blood, especially catecholamines and their metabolites, which have a very similar molecular structure to HVA. They have a very similar molecular structure to HVA, with some having only one functional group difference, making it difficult to distinguish them from HVA and achieve accurate monitoring of blood HVA.Although clinical detection of blood HVA can currently be achieved through high-performance liquid chromatography or enzyme-linked immunosorbent assay (ELISA), real-time monitoring remains challenging due to limitations in blood sampling frequency and quantity, as well as the need for long-term analysis and collection of samples in the laboratory. Therefore, developing a tool for real-time monitoring of HVA in the body remains of great significance.

A highly selective implantable electrochemical fiber optic sensor has been developed to achieve real-time monitoring of HVA in blood. The high selectivity of HVA is achieved through carefully designed molecularly imprinted polymers (MIPs), which only allow molecules that accurately match and recognize binding sites to pass through, providing in vivo selectivity for HVA sensors. The results showed that the selectivity of the sensor towards HVA was 12.6 times higher than that of catecholamines and their metabolites, with an accuracy of 97.8% in vivo.In addition, the biocompatibility of the sensor was evaluated, and no obvious thrombosis, bioadhesion, or inflammation were observed. After minimally invasive injection into the tail vein of rats, the sensor successfully monitored the parallel changes in blood HVA concentration caused by dopamine fluctuations and displayed the excitatory behavior of the rats.

Innovation points

1. The reaction selectivity of molecularly imprinted polymers (MIPs) towards HVA is 12.6 times higher than that of catecholamines and their metabolites;

2. Electrochemical fiber sensors achieve high selectivity and real-time monitoring of high vanillic acid in blood.