Smart needle to diagnose metastatic lymph node using electrical impedance spectroscopy.

OBJECTIVES: The cause of cervical lymphadenopathy varies from inflammation to malignancy. Accurate and prompt diagnosis is crucial as delayed detection of malignant lymph node can lead to a worse prognosis. To improve the diagnostic accuracy of metastatic lymph node, electrical spectroscopy was employed to study human normal and metastatic lymph nodes using a hypodermic needle with fine interdigitated electrodes on its tip (EoN). SUBJECTS AND METHODS: The electrical impedance of samples collected from 8 patients were analyzed in the sweeping frequency range from 1 Hz to 1 MHz. To align the impedance level data of the patients, normalized impedance was employed. RESULTS: The optimal frequency exhibiting the best discrimination results between the normal and cancerous tissues was introduced based on a discrimination index. A high sensitivity (86.2%) and specificity (88.9%) were obtained, which implied that the EoN holds the potential to improve the in vivo diagnostic accuracy of metastatic lymph node during biopsy and surgery. CONCLUSION: EoN has a promising potential to be utilized in real-time in actual clinical trials without a need for any pre/post-treatment during FNA or surgery. We believe that the EoN could reduce unnecessary operations with its associated morbidity.

Facile fabrication of ZnO nanowire memory device based on chemically-treated surface defects.

In this study, we demonstrate a transistor-type ZnO nanowire (NW) memory device based on the surface defect states of a rough ZnO NW, which is obtained by introducing facile H2O2 solution treatment. The surface defect states of the ZnO NW are validated by photoluminescence characterisation. A memory device based on the rough ZnO NW exhibits clearly separated bi-stable states (ON and OFF states). A significant current fluctuation does not exist during repetitive endurance cycling test. Stable memory retention characteristics are also achieved at a high temperature of 85 °C and at room temperature. The surface-treated ZnO NW device also exhibits dynamically well-responsive pulse switching under a sequential pulse test configuration, thereby indicating its potential practical memory applications. The simple chemical treatment strategy can be widely used for modulating the surface states of diverse low-dimensional materials.

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.

Fabrication of Fine Electrodes on the Tip of Hypodermic Needle Using Photoresist Spray Coating and Flexible Photomask for Biomedical Applications.

We have introduced a fabrication method for electrical impedance spectroscopy (EIS)-on-a-needle (EoN: EIS-on-a-needle) to locate target tissues in the body by measuring and analyzing differences in the electrical impedance between dissimilar biotissues. This paper describes the fabrication method of fine interdigitated electrodes (IDEs) at the tip of a hypodermic needle using a photoresist spray coating and flexible film photomask in the photolithography process. A polyethylene terephthalate (PET) heat shrink tube (HST) with a wall thickness of 25 µm is employed as the insulation and passivation layer. The PET HST shows a higher mechanical durability compared with poly(p-xylylene) polymers, which have been widely used as a dielectric coating material. Furthermore, the HST shows good chemical resistance to most acids and bases, which is advantageous for limiting chemical damage to the EoN. The use of the EoN is especially preferred for the characterization of chemicals/biomaterials or fabrication using acidic/basic chemicals. The fabricated gap and width of the IDEs are as small as 20 µm, and the overall width and length of the IDEs are 400 µm and 860 µm, respectively. The fabrication margin from the tip (distance between the tip of hypodermic needle and starting point of the IDEs) of the hypodermic needle is as small as 680 µm, which indicates that unnecessarily excessive invasion into biotissues can be avoided during the electrical impedance measurement. The EoN has a high potential for clinical use, such as for thyroid biopsies and anesthesia drug delivery in a spinal space. Further, even in surgery that involves the partial resection of tumors, the EoN can be employed to preserve as much normal tissue as possible by detecting the surgical margin (normal tissue that is removed with the surgical excision of a tumor) between the normal and lesion tissues.

Evaluation of Electrical Impedance Spectroscopy-on-a-Needle as a Novel Tool to Determine Optimal Surgical Margin in Partial Nephrectomy.

A hypodermic needle has been introduced incorporating an electrical impedance spectroscopy (EIS) sensor, called micro-EIS-on-a-needle for depth profiling (µEoN-DP). The µEoN-DP can locate endophytic renal tumors as well as determine tumor margins by detecting the impedance difference between normal and cancer tissues. To evaluate the µEoN-DP as a novel tool to determine the optimal surgical margin during partial nephrectomy (PN), the electrical impedance differences between renal parenchymal tissues and renal cell carcinoma (RCC) tumors are investigated with regard to the distance from the tumors. Optimal frequencies at which the discrimination extent is maximized are suggested based on the discrimination index. The resistance and capacitance of normal and cancer tissues are extracted using electrical equivalent circuit by excluding the influences of other electrical components on the sensor output. The extracted resistance and capacitance of cancer tissues are 37.8% larger and 25.7% smaller than that of normal tissues, respectively. Additionally, high sensitivity and specificity are obtained by using extracted resistance and capacitance, thus implying that the µEoN-DP shows promise as a supplementary tool for PN margin evaluation and decreasing the prevalence of positive surgical margins while maximizing parenchymal preservation.

Improvement of Depth Profiling into Biotissues Using Micro Electrical Impedance Spectroscopy on a Needle with Selective Passivation.

A micro electrical impedance spectroscopy (EIS)-on-a-needle for depth profiling (µEoN-DP) with a selective passivation layer (SPL) on a hypodermic needle was recently fabricated to measure the electrical impedance of biotissues along with the penetration depths. The SPL of the µEoN-DP enabled the sensing interdigitated electrodes (IDEs) to contribute predominantly to the measurement by reducing the relative influence of the connection lines on the sensor output. The discrimination capability of the µEoN-DP was verified using phosphate-buffered saline (PBS) at various concentration levels. The resistance and capacitance extracted through curve fitting were similar to those theoretically estimated based on the mixing ratio of PBS and deionized water; the maximum discrepancies were 8.02% and 1.85%, respectively. Depth profiling was conducted using four-layered porcine tissue to verify the effectiveness of the discrimination capability of the µEoN-DP. The magnitude and phase between dissimilar porcine tissues (fat and muscle) were clearly discriminated at the optimal frequency of 1 MHz. Two kinds of simulations, one with SPL and the other with complete passivation layer (CPL), were performed, and it was verified that the SPL was advantageous over CPL in the discrimination of biotissues in terms of sensor output.

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.

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).