Showing papers by "Soumen Das published in 2014"

Monitoring cellular activities of cancer cells using impedance sensing devices

Abstract: The present work reports the impedimetric characterization of cellular activities of T47D cells treated with anticancer drug ZD6474 using impedance sensing devices. Four types of devices with different dimensions are fabricated by micromachining technology. Real time impedance monitoring data reveals spreading stage completes within 5 h. The frequency response characteristics of drug treated cells are studied to evaluate cytotoxic effect of ZD6474 along with the sensitivity variation for different designs. Compared to control data, a significant decrease in impedance data is observed for drug treated samples above 10 μM dose due to predominant cell death and detachment from the electrode surfaces. The quantitative relation developed between cell impedance and drug dose indicates that the magnitude of cell impedance varies inversely with the drug dose.

Evaluation of single cell electrical parameters from bioimpedance of a cell suspension

Abstract: The present study introduces a simple and detailed analysis technique to extract the electrical properties of a single cell from the impedance spectroscopy data from a group of cells in suspension, leading to a more reliable and cost effective diagnosis process for disease detection. The existing method for bioimpedance measurement, by trapping a single cell in a microchannel, is quite a complex process and suffers from localized joule heating. Considering that biological cells show their natural characteristics and functionality in a colony of similar cells rather than in an individual environment, the extraction of single cell electrical parameters from the impedance measurement of a group of suspended cells may provide more reliable and effective information. Experimental and theoretical analyses were performed to extract single cell permittivity, conductivity, membrane capacitance and cytoplasm resistance, utilizing the established Maxwell's mixture theory. The bioimpedance of the suspended HeLa cells was characterized with a controlled volume fraction of cells in the suspension, and the measurement was performed by varying the voltage to investigate the change in permittivity and conductivity of the HeLa cells. The proposed technique showed the membrane capacitance and cytoplasm resistance of a single HeLa cell to be in the 1.8 nF cm−2 and 35 kΩ cm2 ranges, respectively. Analysis of the measured impedance data also reveals that the relative permittivity and conductivity of a single HeLa cell is a function of the applied potential and frequency.

Electric cell–substrate impedance sensing technique to monitor cellular behaviours of cancer cells

Abstract: The present work reports the cellular electrical behaviour of the MDA-MB-231 breast cancer cell line treated with the anticancer drug ZD6474, using impedance sensing devices. Microelectrode-based devices with four different electrode geometries are fabricated by microfabrication technology. Real-time impedance monitoring data show high impedance variation during the initial 5 hours, revealing rapid spreading of cells over electrode surfaces. It is further established that impedance variation is mostly controlled by cells covering the electrode surface area, and thus, an enhanced effect is seen with electrode devices with a smaller geometry. Real-time impedimetric cytotoxicity data reveal that cell death and detachment starts at 21 h after inoculation of cells in the devices. The frequency response characteristics of drug-treated cells are studied to evaluate the cytotoxic effect of ZD6474. Compared to the control, a significant variation in the magnitude of the measured impedance data is observed for drug-treated samples above a 5 μM dose, indicating cell growth suppression and cell death. Finally, an empirical relationship between cell impedance and drug dose is established from impedance data, which shows that they are negatively correlated.

Analysis of plasma-induced morphological changes in sputtered thin films over compliant elastomer

Abstract: Flexible electronics and other polymer-based devices demand effective metallization of thin metal films over soft substrates. However, metallization of thin films over soft elastomers such as polydimethylsiloxane (PDMS) often leads to crack formation and morphological changes in the film as well as over the elastomeric surface offering limited applications in the development of biomedical microdevices. In the present study, optimized sputtering conditions like variations in base vacuum, working pressure, sputtering power and time required for crack-free uniform deposition of nichrome thin film over a PDMS surface are discussed. Analysis of film buckling and cracking under optimized and non-optimized conditions is performed through study of plasma colour, optical microphotographs and scanning electron microscopy images. The Young's modulus of an oxidized PDMS surface under no-crack conditions is estimated through the buckling mechanics of thin films and is found to vary with deposition conditions. The present investigation establishes that interaction of a PDMS surface with plasma modifies the surface properties to the extent that its mechanical properties either become compliant to the overlying deposited film, forming buckles, or become noncompliant, leading to cracked films. Fabrication of microheaters on crack-free nichrome thin film under optimized conditions was carried out to explore its suitability in flexible electronics.

Assessing Cytotoxic Effect of ZD6474 on MDA-MB-468 Cells Using Cell-Based Sensor

Abstract: This paper presents the application of an impedance-based measurement of cytotoxicity of ZD6474 on MDA-MB-468 breast cancer cells in culture. In the present experiment, four types of cell-based sensors with different electrode geometries are fabricated by using microfabrication technology. MDA-MB-468 cells are grown on the electrode surfaces to study cell adhesion, spreading, and apoptosis. The real time impedance monitoring data show that the cells took to complete the spreading process on electrode surfaces. The cytotoxic effect of ZD6474 is dose dependant and with the increases of drug doses, the impedance value decreases, which correlates that ZD6474 blocks cell proliferation and induces apoptosis in breast cancer cells. A quantitative relationship, developed between the impedance and drug doses, establishes a negative correlation between the drug doses and impedance. General consistency has been found between the impedance response and the biochemical assay. Thus, impedance sensing method provides a simple and cost effective method to study chemical cytotoxicity in vitro.

Fragmental Frequency Analysis Method to Estimate Electrical Cell Parameters From Bioimpedance Study

Abstract: This paper introduces an alternate approach utilizing the fragmental frequency analysis method for analyzing bioimpedance data to estimate electrical cell parameters. Impedance of cervical cancer cells (HeLa) in phosphate buffer saline media is measured using an electric cell-substrate impedance sensing (ECIS) device and impedance analyzer. The measured impedance data were visualized by modeling an equivalent electrical circuit of the system considering the dominancy of individual parameters of the ECIS system and analyzed in different frequency zones. The present approach eliminates the convergence inaccuracy in fitting the experimental impedance data with fitting software arising due to invalid initial conditions, and a large number of data points. This method provides high-frequency characterization, modeling of ECIS system, knowledge of effect of ECIS model parameters with frequency, and an alternate way to calculate model parameters.

Integrated cervical smear screening using liquid based cytology and bioimpedance analysis.

Abstract: Objective: To minimize the false negativity in cervical cancer screening with Papanicolaou (Pap) test, there is a need to explore novel cytological technique and identification of unique and important cellular features from the perspectives of morphological as well as biophysical properties. Materials and Methods: The present study explores the feasibility of low-cost cervical monolayer techniques in extracting cyto-pathological features to classify normal and abnormal conditions. The cervical cells were also analyzed in respect to their electrical bioimpedance. Result: The results show that newly developed monolayer technique for cervical smears is cost effective, capable of cyto-pathological evaluation. Electrical bioimpedance study evidenced distinction between abnormal and normal cell population at more than two order of magnitude difference. Conclusion: The integration of bioimpedance observation along with the proposed low-cost monolayer technology could increase the efficiency of the cervical screening to a greater extent thereby reducing the rates of faulty diagnosis.

MEMS based normally closed silicon microregulator for gas and water

Abstract: This paper presents the design, fabrication and performance evaluation of a normally closed piezoelectrically actuated silicon microregulator. The microregulator is realized using two wafers process and is designed for the maximum operating pressure 5 bar and it is found to be leak proof (1 × 10 −4 sccm of helium gas).This paper also reports the development of precision fixturing, assembling and testing of the valve. One of the potential areas for application of microregulators is in satellite propulsion using ion thrusters. Ion thrusters require feed systems with very precise propellant gas flow rate and it makes microregulator a suitable candidate. Another application of the microregulator is liquid propellant flow control in micropropulsion. The water flow measurement of the same microregulator is discussed here. The hysteresis measurement of the silicon membrane using inductive probe and the cyclic test of the microregulator are also described here.

Electro-thermal analysis of an embedded boron diffused microheater for thruster applications

Abstract: One of the important design criteria of micropropulsion systems in particular VLM is the type of microheater, its layout and placement with a view to achieve uniform heating of propellant, fast heat transfer efficiency with minimum input power. Thrust produced by microthruster not only depends on the structural geometry of the thruster and propellant flow rate, but also on the chamber temperature to produce super saturated dry stream at the exit nozzle. Detailed design of microheater in thermal and electrical domains using co-solvers available in MEMS software tools along with material’s thermal property, temperature dependence of electrical resistivity and thermal conductivity have been considered in the present work to achieve precise modeling and experimental accuracy of heater operation. The chamber temperature was analytically calculated and subsequently the required resistance and power were estimated. The boron diffused microheaters of meanderline configuration in silicon substrate has been designed and its finite element based electro-thermal modeling was employed to predict the heater characteristics. The variation of microheater temperature with time, applied voltage and along chamber length has been determined from the modeling. Subsequently the designed microheater was realized on silicon wafer by lithography and boron diffusion process and its detailed testing was evaluated. It was found that boron diffused resistor of 820 Ω can generate 405 K temperature with applied input power 2.4 W. Finally the simulated results were validated by experimental data.

Study of PDMS as Dielectric Layer in Electrowetting Devices

Abstract: An electrowetting-on-dielectric (EWOD) device by using Polydimethylsiloxane (PDMS) as dielectric layer has been fabricated. Aluminium metal film is used for EWOD electrode fabrication. Teflon AF 1600 thin film is coated to improve hydrophobicity and reduce liquid sticking (found in PDMS surface). Both PDMS and Teflon layer is deposited by spin coating. Direct coating of Teflon, on top of PDMS layer, results in poor quality film, because of inherent hydrophobic nature of PDMS. So, Oxygen plasma treatment of PDMS surface is carried, before Teflon coating. Movement of water droplet (conductivity: 250 μ S/m) is obtained at 150 V DC voltage supply. Present study demonstrates a simple, cost and time effective fabrication procedure for EWOD device.

SPICE compatible behavioural modelling of resistive sensors

Abstract: In this paper, a modelling technique for anisotropic magneto-resistors (AMRs) and piezo-resistors has been developed. These models are then used to model sensors using such elements. The motivation is to develop a platform which will help in the analysis of different performance parameters of such sensors and optimally design electronic systems for such sensor applications. Non-idealistic behaviour such as temperature and nonlinearity, hysteresis, mismatch, noise, etc have been considered while developing the model. The proposed technique helps us to study each of these non-idealities individually as well as understand the holistic sensor response. Root-cause analysis can, thus, be performed. Model parameters are derived from different product specifications and various characterization reports. The sensor's response predicted from the model is compared with the performance of these products. Response of the model is seen to closely follow the response of the actual product.

Novel architecture for measurements in resistive MEMS sensors

Abstract: A low voltage, low power, resistive sensor architecture is proposed in this paper. The architecture is novel as it enhances the sensitivity along the main axis as well as reducing the impact of cross axes components. The proposed scheme also allows the simultaneous measurement of sensitivity along six different axes. With less than 15% of the power of its Wheatstone bridge [1] counterpart and with a voltage level as low as 2.25 V, this architecture also enables the realization of the sensor using fewer resistive elements. The modified sensor structure, along with the front-end signal processing circuit, is discussed.

Single Silicon Nanowire based Broadband Photodetector with Superior Responsivity

Abstract: Single-silicon-nanowire based MSM photodetectors show superior response (>10000 A/W) even without external bias in visible-to-near-IR region. The responsivity improvement as function of nanowire diameter has been explained by electric-field enhancement using finite-element based optical simulation.

Differential Effect of Isooctane Doses on HaCaT and HeLa: A Multimodal Analysis

Abstract: A multimodal approach is effective in analyzing biological problems critically and thus also useful in assessing cytotoxicity under chemicals assaults. In this study effects of isooctane, an organic solvent and component of gasoline produced in petroleum industries, have been explored on normal (HaCaT) and cancerous (HeLa) epithelial cells. Besides morphological alterations, impacts on viability, prime molecular expressions, and bioelectrical properties on exposure to different doses of isooctane were noted. Scanning electron microscopy and viability assay demonstrated remarkable structural alterations and cell death, respectively, in HaCaT but not in HeLa. Transcriptomic and immunocytochemical studies on E-cadherin expression also elucidated pronounced toxic effects on HaCaT. Remarkable changes on the bioelectrical properties (e.g., impedance and phase angle) of the HaCaT, in contrast to HeLa, at different temporal points on isooctane exposure also indicated cytotoxic effects in the former. Hence this study illustrated cytotoxicity of isooctane on HaCaT multidimensionally which was evaded by HeLa.