Highly sensitive biosensors for real-time monitoring of histamine at acupoint PC6 in rats based on graphene-modified acupuncture needles.

Acupoints are the local initial response sites of acupuncture therapeutic effects. As a biomarker, histamine is released into the acupoint region and plays its role concurrently as acupuncture needles are inserted into acupoints. Hence, real-time monitoring of histamine at acupoints is important to elucidate the effectiveness of the acupoint-activation process in acupuncture. Therefore, we developed highly sensitive acupuncture/Au particles/graphene biosensors by electrodeposition, brushing, and annealing methods based on bare acupuncture needles. We achieved a histamine detection limit of approximately 4.352 (±3.419) × 10 mol L and good sensitivity of approximately 6.296 (±3.873) μA μM, with satisfactory specificity, repeatability, and stability , rendering them more competitive and suitable for real-time monitoring without causing additional damage. Subsequently, we conducted real-time histamine monitoring at non-acupoint and acupoint PC6 in rats, respectively. Our results showed minimal changes at the non-acupoint, whereas a trend of initial increase followed by a decrease was observed at acupoint PC6. The change in histamine concentration at acupoint PC6 reflected its involvement in the acupoint-activation procedure. Moreover, its peak position at ∼18 min could provide guidance for optimizing needle retaining time for maximum therapeutic effect. This work presents the first real-time monitoring of histamine at acupoints with high sensitivity and underscores the specificity of histamine release between non-acupoint and acupoint PC6, demonstrating great potential for elucidating the acupoint-activation mechanisms in acupuncture. Additionally, this work expands the application of nanomaterials in the integration of medicine and engineering, which is an important aspect of the future development of materials science.