Min Haw Wang

Glycated hemoglobin (HbA1c) affinity biosensors with ring-shaped interdigital electrodes on impedance measurement.

Glycated hemoglobin (HbA1c) is one of the most important diagnostic assays for the long-term mark of glycaemic control in diabetes. This study presents an affinity biosensor for HbA1c detection which is label-free based on the impedance measurement, and it features low cost, low sample volume, and requires no additional reagent in experiments. The ring-shaped interdigital electrodes (RSIDEs) are designed to promote the distribution uniformity and immobilization efficiency of HbA1c, and are further employed to characterize the impedance change and identify various concentrations of HbA1c. The self-assembled monolayer (SAM) of thiophene-3-boronic acid (T3BA) is provided to modify the gold electrode surface. Afterwards, the esterification reaction between HbA1c and T3BA produces a relative change of electrical property on the electrode surface. The RSIDEs with SAM of T3BA exhibit a wide range from 100 to 10 ng/µL producing an approximate logarithmic decrease of impedance, a low detection limit of 1 ng/µL, a good selectivity and short-term stability for HbA1c determination. The remarkable advantages (miniaturization and low-cost) fill the bill of point-care diagnostics for portable sensor development.

A systematic investigation into the electrical properties of single HeLa cells via impedance measurements and COMSOL simulations.

The electrical properties of single cells provide fundamental insights into their pathological condition and are therefore of immense interest to medical practitioners. Accordingly, this study captures single HeLa cells using a microfluidic device and then measures their impedance properties using a commercial impedance spectroscopy system. The experimental system is modeled by an equivalent electrical circuit and COMSOL simulations are then performed to establish the conductivity, permittivity and impedance of single HeLa cells under various operational frequencies and voltages. At an operational voltage of 0.2 V, the maximum deviation between the experimental and simulation results for the magnitude and phase of the HeLa cell impedance is found to be 9.5% and 4.2%, respectively. In general, both sets of results show that the conductivity and permittivity of single HeLa cells increase with an increasing operational voltage. Moreover, an increasing frequency is found to increase the conductivity of HeLa cells at all values of the operational voltage, but to reduce the permittivity for operational voltages in the range 0.6-1.0 V. Based upon the simulation and experimental results, empirical equations are constructed to predict the conductivity and permittivity of single HeLa cells under specified values of the operational voltage and frequency, respectively. The maximum discrepancy between the predicted results and the simulation results for the permittivity and conductivity of the HeLa cells at an operational voltage of 0.2 V is found to be just 0.5% and 4.5%, respectively.

Single HeLa and MCF-7 cell measurement using minimized impedance spectroscopy and microfluidic device

This study presents an impedance measurement system for single-cell capture and measurement. The microwell structure which utilizes nDEP force is used to single-cell capture and a minimized impedance spectroscopy which includes a power supply chip, an impedance measurement chip and a USB microcontroller chip is used to single-cell impedance measurement. To improve the measurement accuracy of the proposed system, Biquadratic fitting is used in this study. The measurement accuracy and reliability of the proposed system are compared to those of a conventional precision impedance analyzer. Moreover, a stable material, latex beads, is used to study the impedance measurement using the minimized impedance spectroscopy with cell-trapping device. Finally, the proposed system is used to measure the impedance of HeLa cells and MCF-7 cells. The impedance of single HeLa cells decreased from 9.55 × 10(3) to 3.36 × 10(3) Ω and the impedance of single MCF-7 cells decreased from 3.48 × 10(3) to 1.45 × 10(3) Ω at an operate voltage of 0.5 V when the excitation frequency was increased from 11 to 101 kHz. The results demonstrate that the proposed impedance measurement system successfully distinguishes HeLa cells and MCF-7 cells.

Battery‐powered portable instrument system for single‐cell trapping, impedance measurements, and modeling analyses

A battery‐powered portable instrument system for the single‐HeLa‐cell trapping and analyses is developed. A method of alternating current electrothermal (ACET) and DEP are employed for the cell trapping and the method of impedance spectroscopy is employed for cell characterizations. The proposed instrument (160 mm × 170 mm × 110 mm, 1269 g) equips with a highly efficient energy‐saving design that promises approximately 120 h of use. It includes an impedance analyzer performing an excitation voltage of 0.2–2 Vpp and a frequency sweep of 11–101 kHz, function generator with the sine wave output at an operating voltage of 1–50 Vpp with a frequency of 4–12 MHz, cell‐trapping biochip, microscope, and input/output interface. The biochip for the single cell trapping is designed and simulated based on a combination of ACET and DEP forces. In order to improve measurement accuracy, the curve fitting method is adopted to calibrate the proposed impedance spectroscopy. Measurement results from the proposed system are compared with results from a precision impedance analyzer. The trapped cell can be modeled for numerical analyses. Many advantages are offered in the proposed instrument such as the small volume, real‐time monitoring, rapid analysis, low cost, low‐power consumption, and portable application.

Experimental analysis of time-phase-shift flow sensing based on a piezoelectric peristaltic micropump

Flow rate sensing is a critical issue for piezoelectric-based micropump systems. This paper describes experimental analysis of flow rate sensing in a peristaltic micropump system. Sensing can be integrated with such a pump using piezoelectric actuators based on the time-phase-shift (TPS) method. To do this, an evaluation-window is added on the falling edge of the driving pulse to help detect the flow velocity without affecting the flow rate. We fabricate a prototype piezoelectric peristaltic micropump with three chambers and three piezoelectric actuators. The middle actuator works not only as an actuator for driving fluid but also as a transducer for sensing flow rate. An evaluation-window is performed to ascertain the relationship between the flow rate and the phase shift of output-signal responses from the transducer. The experimental results show that the evaluation-window response of flow rates in a piezoelectric peristaltic micropump has rates of from 5.56‒33.36 μl s−1. The results are extended to propose a practical flow rate sensor, the design of which can be realized easily in the piezoelectric peristaltic micropump system for sensorless responses that can detect flow rate without any sensors or circuits. The proposed TPS method is real-time, integrated, fast, efficient, and suitable for flow rate detection in piezoelectric peristaltic micropumps.

Highly sensitive three-dimensional interdigitated microelectrode for microparticle detection using electrical impedance spectroscopy

Cell impedance analysis is widely used for monitoring biological and medical reactions. In this study, a highly sensitive three-dimensional (3D) interdigitated microelectrode (IME) with a high aspect ratio on a polyimide (PI) flexible substrate was fabricated for microparticle detection (e.g. cell quantity detection) using electroforming and lithography technology. 3D finite element simulations were performed to compare the performance of the 3D IME (in terms of sensitivity and signal-to-noise ratio) to that of a planar IME for particles in the sensing area. Various quantities of particles were captured in Dulbeccos modified Eagle medium and their impedances were measured. With the 3D IME, the particles were arranged in the gap, not on the electrode, avoiding the noise due to particle position. For the maximum particle quantities, the results show that the 3D IME has at least 5-fold higher sensitivity than that of the planar IME. The trends of impedance magnitude and phase due to particle quantity were verified using the equivalent circuit model. The impedance (1269 Ω) of 69 particles was used to estimate the particle quantity (68 particles) with 98.6% accuracy using a parabolic regression curve at 500 kHz.

Effect of cell position on impedance measurement in microfluidic channel with planar microelectrodes and a three-pillar structure

Impedance analysis of single cells offers the possibility of obtaining accurate, reliable, and in-depth information about their pathological condition. In this work, we present the physical capture of a single cell using a microfluidic device with a three-pillar microstructure, impedance measurement using a set of planar microelectrodes, and the derivation of an electrical model that fits the experimental results. The relationship between impedance characteristics and the location of a single HeLa cell (human cervical epithelioid carcinoma) is investigated by impedance spectroscopy. When a single cell fell toward the electrodes after it has been trapped by the three-pillar microstructure, the impedance and the phase change are measured in an operating frequency range of 1 to 100 kHz. The equivalent circuit model is established and two elements that depend on cell location are used to investigate the impedance change of a single HeLa cell.

Dual-wavelength optical fluidic glucose sensor using time series analysis of d(+)-glucose measurement

This paper presents a rising-edge time-series analysis (TSA) method that can be applied to a dual-wavelength optical fluidic glucose sensor (DWOFGS). In the experiment, the concentration of glucose in phosphate buffered saline (PBS) was determined by measuring the absorbance of the solution as determined by variation in the rising edge of the photodiode (PD) voltage response waveform. The DWOFGS principle is based on near-infrared (NIR) absorption spectroscopy at selected dual wavelengths (1450 and 1650 nm) in the first overtone band. The DWOFGS comprises two light-emitting diodes (LEDs) and two PD detectors. No additional fibers or lenses are required in our device. The output light level of the LEDs is adjusted to a light intensity suitable to the glucose absorption rate in an electronic circuit. Four light absorbance paths enable detection of d(+)-glucose concentrations from 0 to 20 wt % in steps of 5 wt %. The glucose light absorbance process was calculated based on the rising edge of the PD waveform under a low-intensity light source using TSA. The TSA method can be used to obtain the glucose level in PBS and reduce measurement background noise. The application of the rising-edge TSA method improves sensor sensitivity, increases the accuracy of the data analysis, and lowers measurement equipment costs.