Department of Electronics and Telecommunications (DET), Politecnico di Torino, Corso Duca degli Abruzzi, 24, 10129 Turin, Italy.
Institute of Biostructure and Bioimaging (CNR), Molecular Biotechnology Center (MBC), Via Nizza, 52, 10126 Turin, Italy.
Biosensors (Basel). 2022 Feb 13;12(2):116. doi: 10.3390/bios12020116.
Liver fibrosis is a key pathological precondition for hepatocellular carcinoma in which the severity is confidently correlated with liver cancer. Liver fibrosis, characterized by gradual cell loss and excessive extracellular matrix deposition, can be reverted if detected at the early stage. The gold standard for staging and diagnosis of liver fibrosis is undoubtedly biopsy. However, this technique needs careful sample preparation and expert analysis. In the present work, an ex vivo, minimally destructive, label-free characterization of liver biopsies is presented. Through a custom-made experimental setup, liver biopsies of bile-duct-ligated and sham-operated mice were measured at 8, 15, and 21 days after the procedure. Changes in impedance were observed with the progression of fibrosis, and through data fitting, tissue biopsies were approximated to an equivalent RC circuit model. The model was validated by means of 3D hepatic cell culture measurement, in which the capacitive part of impedance was proportionally associated with cell number and the resistive one was proportionally associated with the extracellular matrix. While the sham-operated samples presented a decrease in resistance with time, the bile-duct-ligated ones exhibited an increase in this parameter with the evolution of fibrosis. Moreover, since the largest difference in resistance between healthy and fibrotic tissue, of around 2 kΩ, was found at 8 days, this method presents great potential for the study of fibrotic tissue at early stages. Our data point out the great potential of exploiting the proposed needle setup in clinical applications.
肝纤维化是肝细胞癌的关键病理前提，其严重程度与肝癌密切相关。如果在早期发现，肝纤维化是可以逆转的。肝纤维化的分期和诊断的金标准无疑是肝活检。然而，这项技术需要仔细的样本制备和专家分析。在本工作中，提出了一种离体、微创、无标记的肝活检特征描述方法。通过定制的实验装置，在手术后 8、15 和 21 天测量了胆管结扎和假手术小鼠的肝活检。随着纤维化的进展，观察到阻抗的变化，并通过数据拟合，将组织活检近似为等效 RC 电路模型。通过 3D 肝细胞培养测量对模型进行了验证，其中阻抗的电容部分与细胞数量成比例相关，而电阻部分与细胞外基质成比例相关。虽然假手术样本的电阻随时间呈下降趋势，但胆管结扎样本的电阻随纤维化的发展呈上升趋势。此外，由于在 8 天时健康组织和纤维化组织之间的电阻最大差异（约 2 kΩ），因此该方法在早期纤维化组织研究中具有很大的潜力。我们的数据指出了在临床应用中利用所提出的针设置的巨大潜力。
