Microfabrication and application of minimally invasive sensors to evaluation of electrical properties of bio-tissues in depth profiling

Abstract

Biopsy (purpose: a pathological examination of lesions) and percutaneous ethanol injection (PEI) (purpose: non-surgical treatment of hepatocellular carcinoma) in the liver are widely performed using a fine needle under ultrasonography (US) guidance. Since the US guidance, however, exhibits low specificity and low sensitivity, there is a problem in distinguishing a malignant tumor from parenchyma in ultrasonography. This study proposes a method for identifying the malignant tumor from the parenchyma using coplanar bipolar electrodes fabricated on a fine needle, called EIS-on-a-needle (EoN). Here, the electrodes of EoN were comprised of a detection part and a connection part. The distance between the detection part and the sharp tip (DET) in EoN was fabricated as short as 280 μm to minimize the intrahepatic vascular damage due to the unnecessarily excessive penetration. The total length of the detection part was designed to be 460 μm, which is a better resolution than ultrasonography (e.g. 0.5 mm). Meanwhile, the connection part of EoN was selectively coated using PET (polyethylene terephthalate) tube to reduce the distortion in the electrical impedance according to the penetration depth. An incremental compensation method (ICM) was also applied to the sensor output for the enhancement of detection accuracy in depth-profiling. The electrical impedances of the malignant tumors and parenchyma were measured in two pathological statuses, more specifically in human ex-vivo normal liver and in human ex-vivo cirrhotic liver. Statistically significant differences in the electrical impedance between the malignant tumor and parenchyma in each pathological status were exhibited in common over the high-frequency range (400 kHz ~ 1 MHz), such as p-value under 0.05. To generalize the sensor output, the electrical properties (conductivity and permittivity) of tissues were estimated using ICM experimentally verified to enhance the detection accuracy in depth-profiling, regardless of the dimension and shape of the electrodes. The electrical properties between malignant tumors and parenchyma were significantly different in each pathological status, such as P-value under 0.05. These experimental results (the differences in the electrical impedance and electrical properties) imply that EoN can be used as potential guidance for the identification of malignant tumors in the liver during biopsy and PEI procedures.