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%.

Enhanced nanoplasmonic heating in standoff sensing of explosive residues with infrared reflection-absorption spectroscopy.

Various standoff sensing techniques employing optical spectroscopy have been developed to address challenges in safely identifying trace amounts of explosives at a distance. A flexible anodic aluminum oxide (AAO) microcantilever and a high-power quantum cascade laser utilized as the infrared (IR) source are used for standoff IR reflection-absorption spectroscopy to detect explosive residues on a metal surface. Standoff sensing of trinitrotoluene (TNT) is demonstrated by exploiting the high thermomechanical sensitivity of a bimetallic AAO microcantilever. Moreover, sputtering gold onto the fabricated AAO nanowells generates a strong scattering and absorption of IR light in the wavelength range of 5.18 µm to 5.85 µm resulting in enhanced nanoplasmonic heating. Utilizing the IR absorption enhancement in this wavelength range, the plasmonic AAO cantilever could detect TNT molecules 7 times better than could the bimetallic AAO cantilever.

Large-scale transfer of Ag nanowires from PET to PC film using a roll-to-roll UV lamination process for a capacitive touch sensor.

Demand for flexible transparent sensors for futuristic cars is increasing since such sensors can enhance the freedom of design and aesthetic value in the interior of cars. Herein, we propose a unique roll-to-roll UV lamination process that can expedite large-scale Ag nanowire (AgNW) transfer for a flexible capacitive sensor, using a photocurable resin composed of an epoxy acrylate oligomer, a reactive monomer (1,6-hexanediol diacrylate), and a photoinitiator (1-hydroxycyclohexyl phenyl ketone). The acryl groups in the resin were rapidly crosslinked by UV irradiation, which facilitated the AgNWs transfer from a PET to a PC substrate with the speed of 1050 cm2 min-1 and enhanced the adhesion between the AgNWs and the PC substrate. Systematic experiments were performed to determine optimal fabrication parameters with respect to the UV dose, lamination pressure, and laser dicing conditions. At the optimal fabrication conditions, the sheet resistance of AgNWs on a PC film (PC-AgNW) was as small as 36.79 Ω sq-1, which was only 3.17% deviation from that on a PET film (PET-AgNW). Furthermore, the optical transmittance of the PC-AgNW exceeded 88% over the visible range, and it was greater than that of the PET-AgNW. Notably, the sheet resistance of the PC-AgNW was almost constant after 50 taping and peeling cycles, indicating remarkable adhesion to the substrate. Furthermore, a capacitive touch sensor was fabricated using the PC-AgNW, and its switching signals were presented with and without finger touch.

Input Shaping Based on an Experimental Transfer Function for an Electrostatic Microscanner in a Quasistatic Mode.

This paper describes an input shaping method based on an experimental transfer function to effectively obtain a desired scan output for an electrostatic microscanner driven in a quasistatic mode. This method features possible driving extended to a higher frequency, whereas the conventional control needs dynamic modeling and is still ineffective in mitigating harmonics, sub-resonances, and/or higher modes. The performance of the input shaping was experimentally evaluated in terms of the usable scan range (USR), and its application limits were examined with respect to the optical scan angle and frequency. The experimental results showed that the usable scan range is as wide as 96% for a total optical scan angle (total OSA) of up to 9° when the criterion for scan line error is 1.5%. The usable scan ranges were degraded for larger total optical scan angles because of the nonlinear electrostatic torque with respect to the driving voltage. The usable scan range was 90% or higher for most frequencies up to 160 Hz and was drastically decreased for the higher driving frequency because fewer harmonics are included in the input shaping process. Conclusively, the proposed method was experimentally confirmed to show good performance in view of its simplicity and its operable range, quantitatively compared with that of the conventional control.

Detection of ischemic changes in the vascular endothelial cell layer by using microelectrochemical impedance spectroscopy.

Endothelial cells have many important roles in the cardiovascular system, such as controlling vasomotor actions and hemostasis. In the event of endothelial cell dysfunction, the risk of cardiovascular disease increases. Therefore, the objective of this study was to investigate the early detection and diagnosis of endothelial cell dysfunction. Injury and restoration in vascular endothelial cells exposed to ischemic stress may affect changes in the electrical impedance. We measured the status of the endothelial cell layer by using microelectrochemical impedance spectroscopy. We used cultured rat primary vascular endothelial cells to measure the electrical impedance under different conditions (control, ischemia, and recovery). Our results revealed that the electrical impedance in vascular endothelial cells under different conditions has quantitatively distinct values. At the optimal frequency, the real parts (ZR) of the impedances for the control group, ischemic group, and recovery group were 0.54 kΩ, 0.28 kΩ, and 0.58 kΩ, respectively. The imaginary parts (ZI) of the impedances for each group were - 0.19 kΩ, - 0.12 kΩ, and - 0.18 kΩ, respectively. The values for both the recovery group and control group were similar. In this context, electrical impedance measurement could be considered as possible method for direct detection of vascular endothelial cell injury in ischemic conditions. To the best of our knowledge, this study is the first attempt to measure changes in the electrical impedance of vascular endothelial cells during ischemic damage and the recovery processes.

Gimbal-Less Two-Axis Electromagnetic Microscanner with Twist Mechanism.

We present an electromagnetically driven microscanner based on a gimbal-less twist mechanism. In contrast to conventional microscanners using a gimbal-less leverage mechanism, our device utilizes a gimbal-less twist mechanism to increase the scan angle in optical applications requiring a large scanning mirror. The proposed gimbal-less scanner with twist mechanism increases the scan angle by 1.55 and 1.97 times for the slow and fast axes, respectively, under the same force; 3.64 and 1.97 times for the slow and fast axes, respectively, under the same maximum stress, compared to the gimbal-less leverage mechanism. The scanner with a 3-mm-diameter mirror and a current path composed of a single-turn coil was fabricated, and it showed the maximum scan angle of 5° (quasi-static) and 22° (resonant) for the slow and fast axes, respectively. The experimentally estimated crosstalk was as small as 0.47% and 0.97% for the fast and slow axes affected by the other axes, respectively, which was determined using a newly employed methodology based on fast Fourier transform.

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.

Ex vivo characterization of age-associated impedance changes of single vascular endothelial cells using micro electrical impedance spectroscopy with a cell trap.

We aimed to characterize aging of single vascular endothelial cells, which are indicators of senescence, using micro electrical impedance spectroscopy (µEIS) for the first time. The proposed µEIS was equipped with two barriers under the membrane actuator near the sensing electrodes, increasing its cell-trapping capability and minimizing the interference between the target cell and subsequent cells. The cell-trapping capability in µEIS with barriers was considerably improved (90%) with a capture time of 5 s or less, compared to µEIS without barriers (30%). Cells were extracted from transgenic zebrafish to minimize an initial discrepancy originating from genetic differences. In order to estimate useful parameters, cytoplasm resistance and membrane capacitance were estimated by fitting an electrical equivalent circuit to the data of ex vivo sensor output. The estimated cytoplasm resistance and membrane capacitance in the younger vascular endothelial cells were 20.16 ± 0.79 kΩ and 17.46 ± 0.76 pF, respectively, whereas those in the older cells were 17.81 ± 0.98 kΩ and 20.08 ± 1.38 pF, respectively. Discrimination of each group with different aging showed statistical significance in terms of cytoplasm resistance (p < 0.001) and membrane capacitance (p < 0.001). Considering both of the sensor and cellular level, the optimal frequency was determined as 1 MHz at which the electrical impedance of each group was clearly discriminated (p < 0.001).

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.

Cell Electrical Impedance as a Novel Approach for Studies on Senescence Not Based on Biomarkers.

Senescence of cardiac myocytes is frequently associated with heart diseases. To analyze senescence in cardiac myocytes, a number of biomarkers have been isolated. However, due to the complex nature of senescence, multiple markers are required for a single assay to accurately depict complex physiological changes associated with senescence. In single cells, changes in both cytoplasm and cell membrane during senescence can affect the changes in electrical impedance. Based on this phenomenon, we developed MEDoS, a novel microelectrochemical impedance spectroscopy for diagnosis of senescence, which allows us to precisely measure quantitative changes in electrical properties of aging cells. Using cardiac myocytes isolated from 3-, 6-, and 18-month-old isogenic zebrafish, we examined the efficacy of MEDoS and showed that MEDoS can identify discernible changes in electrical impedance. Taken together, our data demonstrated that electrical impedance in cells at different ages is distinct with quantitative values; these results were comparable with previously reported ones. Therefore, we propose that MEDoS be used as a new biomarker-independent methodology to obtain quantitative data on the biological senescence status of individual cells.

Anti-Reflux Ureteral Stent with Polymeric Flap Valve Using Three-Dimensional Printing: An In Vitro Study.

PURPOSE: This article aims to describe the design of an anti-reflux ureteral stent with a polymeric flap valve and the fabrication methods using three-dimensional (3D) printing. The stent effectively prevents backward flow with a negligible reduction in forward flow. Fabrication of miniaturized valves was easy with high precision and rapid prototyping. MATERIALS AND METHODS: The proposed stent comprised a 7F Double-J (DJ) stent and a polymeric flap valve. The valve was made of Tango Plus FLX980 and was fabricated using a 3D printer. Two types of stent were prepared for in vitro tests: DJ stents with (1) an uncoated valve (UCV) stent and (2) a parylene C coated valve (PCV) stent for enhanced biocompatibility. The flow characteristics of each stent were evaluated considering flow direction, parylene coating, and stent side holes, and were compared to the intact DJ stent. RESULTS: The forward flow rate for the distal portion of the UCV and PCV stents was 9.8 mL/min and 7.8 mL/min at applied pressure of 15 cm H2O (normal anterograde pressure in patients with stents), respectively. Backward flow rate for the distal portion of the UCV and PCV stents was decreased by 28 times and 8 times at applied pressure of 50 cm H2O (maximum bladder pressure), respectively, compared with the distal portion of the intact DJ stent. Forward flow rates of whole stents were 22.2 mL/min (UCV stent) and 20.0 mL/min (PCV stent) at applied pressure of 15 cm H2O, and backward flow rates of whole UCV and PCV stents were decreased by 8.3 times and 4.0 times at applied pressure of 50 cm H2O, respectively, compared with the intact DJ stent. CONCLUSIONS: The anti-reflux ureteral stent was successfully designed and fabricated using a 3D printer. In vitro studies showed that the stent effectively prevented backward flow while minimizing reduction in forward flow.