Classification between Normal and Cancerous Human Urothelial Cells by Using Micro-Dimensional Electrochemical Impedance Spectroscopy Combined with Machine Learning.

Although the high incidence and recurrence rates of urothelial cancer of the bladder (UCB) are heavy burdens, a noninvasive tool for effectively detecting UCB as an alternative to voided urine cytology, which has low sensitivity, is yet to be reported. Herein, we propose an intelligent discrimination method between normal (SV-HUC-1) and cancerous (TCCSUP) urothelial cells by using a combination of micro-dimensional electrochemical impedance spectroscopy (µEIS) with machine learning (ML) for a noninvasive and high-accuracy UCB diagnostic tool. We developed a unique valved flow cytometry, equipped with a pneumatic valve to increase sensitivity without cell clogging. Since contact between a cell and electrodes is tight with a high volume fraction, the electric field can be effectively confined to the cell. This enables the proposed sensor to highly discriminate different cell types at frequencies of 10, 50, 100, 500 kHz, and 1 MHz. A total of 236 impedance spectra were applied to six ML models, and systematic comparisons of the ML models were carried out. The hyperparameters were estimated by conducting a grid search or Bayesian optimization. Among the ML models, random forest strongly discriminated between SV-HUC-1 and TCCSUP, with an accuracy of 91.7%, sensitivity of 92.9%, precision of 92.9%, specificity of 90%, and F1-score of 93.8%.

Micro electrical impedance spectroscopy on a needle for ex vivo discrimination between human normal and cancer renal tissues.

The ex-vivo discrimination between human normal and cancer renal tissues was confirmed using µEoN (micro electrical impedance spectroscopy-on-a-needle) by measuring and comparing the electrical impedances in the frequency domain. To quantify the extent of discrimination between dissimilar tissues and to determine the optimal frequency at which the discrimination capability is at a maximum, discrimination index (DI) was employed for both magnitude and phase. The highest values of DI for the magnitude and phase were 5.15 at 1 MHz and 3.57 at 1 kHz, respectively. The mean magnitude and phase measured at the optimal frequency for normal tissues were 5013.40 ± 94.39 Ω and -68.54 ± 0.72°, respectively; those for cancer tissues were 4165.19 ± 70.32 Ω and -64.10 ± 0.52°, respectively. A statistically significant difference (p< 0.05) between the two tissues was observed at all the investigated frequencies. To extract the electrical properties (resistance and capacitance) of these bio-tissues through curve fitting with experimental results, an equivalent circuit was proposed based on the µEoN structure on the condition that the µEoN was immersed in the bio-tissues. The average and standard deviation of the extracted resistance and capacitance for the normal tissues were 6.22 ± 0.24 kΩ and 280.21 ± 32.25 pF, respectively, and those for the cancer tissues were 5.45 ± 0.22 kΩ and 376.32 ± 34.14 pF, respectively. The electrical impedance was higher in the normal tissues compared with the cancer tissues. The µEoN could clearly discriminate between normal and cancer tissues by comparing the results at the optimal frequency (magnitude and phase) and those of the curve fitting (extracted resistance and capacitance).

Microelectrical Impedance Spectroscopy for the Differentiation between Normal and Cancerous Human Urothelial Cell Lines: Real-Time Electrical Impedance Measurement at an Optimal Frequency.

PURPOSE: To distinguish between normal (SV-HUC-1) and cancerous (TCCSUP) human urothelial cell lines using microelectrical impedance spectroscopy (µEIS). MATERIALS AND METHODS: Two types of µEIS devices were designed and used in combination to measure the impedance of SV-HUC-1 and TCCSUP cells flowing through the channels of the devices. The first device (µEIS-OF) was designed to determine the optimal frequency at which the impedance of two cell lines is most distinguishable. The µEIS-OF trapped the flowing cells and measured their impedance at a frequency ranging from 5 kHz to 1 MHz. The second device (µEIS-RT) was designed for real-time impedance measurement of the cells at the optimal frequency. The impedance was measured instantaneously as the cells passed the sensing electrodes of µEIS-RT. RESULTS: The optimal frequency, which maximized the average difference of the amplitude and phase angle between the two cell lines (p < 0.001), was determined to be 119 kHz. The real-time impedance of the cell lines was measured at 119 kHz; the two cell lines differed significantly in terms of amplitude and phase angle (p < 0.001). CONCLUSION: The µEIS-RT can discriminate SV-HUC-1 and TCCSUP cells by measuring the impedance at the optimal frequency determined by the µEIS-OF.

Evaluation of a Polymeric Flap Valve-Attached Ureteral Stent for Preventing Vesicoureteral Reflux in Elevated Intravesical Pressure Conditions: A Pilot Study Using a Porcine Model.

OBJECTIVE: To evaluate the effectiveness of a polymeric flap valve-attached ureteral stent for preventing vesicoureteral reflux (VUR) in an animal model. MATERIALS AND METHODS: One female Yorkshire pig was included in this study. A flap valve-attached and a conventional stent was inserted in the right and left ureters, respectively. The bladder was filled with contrast medium until the intravesical pressure reached 20 cm H2O. Subsequently, simulated voiding cystourethrography (VCUG) was performed 50 times by manually compressing the suprapubic area until the intravesical pressure reached 50 cm H2O. Intravenous pyelography (IVP) was performed thereafter to evaluate the urinary drainage. In addition, an in vitro durability test of the function of the flap valve was conducted under continuous hydrostatic pressure for 24 h. RESULTS: The volume of contrast medium needed to achieve an intravesical pressure of 20 cm H2O was 1740 mL. In the repeated simulated VCUG for the right ureter, VUR grades of 0 and I were recorded in 82.0 (n = 41) and 18.0% (n = 9) tests, respectively, whereas for the left ureter, grades of I, II, and III were recorded in 14.0 (n = 7), 82.0 (n = 41), and 4.0% (n = 2), respectively. Thus, a significantly lower VUR grade was recorded for the right ureter than for the left ureter (p < 0.001). In the bilateral VUR condition, the pressure for VUR occurrence was significantly greater in the right ureter than in the left ureter (p = 0.007). No urinary obstruction was caused by the flap valve-attached ureteral stent according to the IVP findings. The in vitro durability test demonstrated slightly enhanced antireflux function and slightly decreased intraluminal drainage at 12 h, and these findings sustained thereafter. CONCLUSION: A flap valve-attached ureteral stent effectively prevented VUR under conditions of elevated intravesical pressure without urinary obstruction.