Development of a plasma injection probe for deep tissue drug analysis

Abstract

Anticancer drugs and other pharmaceuticals achieve maximal therapeutic efficacy with minimal side effects when delivered to the target site at an appropriate concentration. Accordingly, quantifying the amount of drug reaching the target tissue is essential for evaluating pharmacological effectiveness. However, direct measurement of a drug concentration within specific tissues in vivo remains technically challenging. In this study, a plasma injection probe incorporating an ultra-small plasma source inside a syringe needle was developed, and its fundamental performance was evaluated using 4-isopropylantipyrine as a model analyte. First, an ultra-small plasma source with an outer diameter of approximately 700 µm, suitable for integration into an injection needle, was fabricated. Plasma irradiation of a biological tissue-mimicking sample surface demonstrated that helium yielded the highest signal intensity among the tested plasma generation gases. In addition, the introduction of 2% hydrogen further enhanced analytical sensitivity. The measured gas temperature was approximately 22–23 °C, indicating suitability for potential in vivo application. Subsequently, the plasma injection probe was inserted into a biological tissue-mimicking sample to evaluate its capability to detect drugs within the sample interior. When the plasma gas flow rate was varied, the signal intensity reached a maximum at 100 mL min⁻¹, and the limit of detection was approximately 10 ppm. Furthermore, the depth resolution of the plasma injection probe was determined to be 0.4 mm.