Hsiu-Li Shieh

Carbon nanotube composites for glucose biosensor incorporated with reverse iontophoresis function for noninvasive glucose monitoring.

This study aims to develop an amperometric glucose biosensor, based on carbon nanotubes material for reverse iontophoresis, fabricated by immobilizing a mixture of glucose oxidase (GOD) and multiwalled carbon nanotubes (MWCNT) epoxy-composite, on a planar screen-printed carbon electrode. MWCNT was employed to ensure proper incorporation into the epoxy mixture and faster electron transfer between the GOD and the transducer. Results showed this biosensor possesses a low detection potential (+500 mV), good sensitivity (4 μA/mM) and an excellent linear response range (r2 = 0.999; 0–4 mM) of glucose detection at +500 mV (versus Ag/AgCl). The response time of the biosensor was about 25 s. In addition, the biosensor could be used in conjunction with reverse iontophoresis technique. In an actual evaluation model, an excellent linear relationship (r2 = 0.986) was found between the glucose concentration of the actual model and the biosensor’s current response. Thus, a glucose biosensor based on carbon nanotube composites and incorporated with reverse iontophoresis function was developed.

The use of bioimpedance in the detection/screening of tongue cancer

Oral cancers are the 11th most common malignancy reported worldwide, accounting for 3% of all newly diagnosed cancer cases, and one with high mortality ratios among all malignancies. The objectives of this study were therefore to study the electrical properties of cancerous tongue tissue and normal tongue tissue, as well as to investigate a new approach for low-cost, noninvasive, and real-time screening of oral cancer. Twelve tongue cancer patients and twelve healthy subjects participated in this study. A disposable probe with four silver electrodes was used to measure the electrical properties of patients and healthy subjects tongue tissues at six different frequencies, which were 20Hz, 50kHz, 1.3MHz, 2.5MHz, 3.7MHz and 5MHz. The amplitude of the applied voltage was limited to 200mV. Four measurement parameters of impedance, phase angle, real part of impedance, and imaginary part of impedance of tongue were assessed to see if significant difference in values obtained in patients and healthy subjects tongue tissues existed. Intraclass correlation coefficient showed that all measurements had good reliability and validity (ICC>0.95 for all measurements). Significant differences were found at 20Hz (p<0.05-0.001 for the four measurement parameters) and 50kHz (p<0.001 for the four measurement parameters) between patients and healthy subjects tongue tissues. In conclusion, bioimpedance at a particular frequency is a potentially promising technique for tongue cancer screening.

Characterization of the Muscle Electrical Properties in Low Back Pain Patients by Electrical Impedance Myography

Objectives This study aims to investigate the electrical properties of lumbar paraspinal muscles (LPM) of patients with acute lower back pain (LBP) and to study a new approach, namely Electrical Impedance Myography (EIM), for reliable, low-cost, non-invasive, and real-time assessment of muscle-strained acute LBP. Design Patients with muscle-strained acute LBP (n = 30) are compared to a healthy reference group (n = 30). Electrical properties of LPM are studied. Background EIM is a novel technique under development for the assessment of neuromuscular disease. Therefore, it is speculated that EIM can be employed for the assessment of muscle-strained acute LBP. Methods Surface electrodes, in 2-electrode configurations, was used to measure the electrical properties of patients and healthy subjects LPM at six different frequencies (0.02, 25.02, 50.02, 1000.02, 3000.02, and 5000.02 kHz), with the amplitude of the applied voltage limited to 200 mV. Parameters of impedance (Z), extracellular resistance (Re), intracellular resistance (Ri), and the ratio of extracellular resistance to intracellular resistance (Re/Ri) of LBP patients and healthy subjects LPM were assessed to see if significant difference in values obtained in muscle-strained acute LBP patients existed. Results Intraclass correlation coefficient (ICC) showed that all measurements (ICC>0.96 for all studying parameters: Z, Re, Ri, and Re/Ri) had good reliability and validity. Significant differences were found on Z between LBP patients and healthy subjects LPM at all studying frequencies, with p<0.05 for all frequencies. It was also found that Re (p<0.05) and Re/Ri (p<0.05) of LBP patients LPM was significant smaller than that of healthy subjects while Ri (p<0.05) of LBP patients LPM was significant greater than that of healthy subjects. No statistical significant difference was found between the left and right LPM of LBP patients and healthy subjects on the four studying parameters. Conclusion EIM is a promising technique for assessing muscle-strained acute LBP.

A preliminary study of the use of bioimpedance in the screening of squamous tongue cancer

Oral cancers are the 11th most common malignancy reported worldwide, accounting for 3% of all newly diagnosed cancer cases, and one with high mortality ratios among all malignancies. The objective of this study was to study the electrical properties of cancerous tongue tissue (CTT) and normal tongue tissue (NTT). Five tongue cancer patients participated in this study. A disposable probe incorporating four silver electrodes was used to measure the electrical properties of CTT and the surrounding NTT of patients. Measurements were performed at six frequencies: 20 Hz; 50 kHz; 1.3 MHz; 2.5 MHz; 3.7 MHz; and 5 MHz, with the amplitude of the applied voltage limited to 200mV. Four measurement parameters of impedance (Z), phase angle (θ), real part of impedance (R), and imaginary part of impedance (X) of tongue tissue were assessed to see if there was any significant difference in the values obtained in CTT and surrounding NTT. The intraclass correlation coefficient showed that all measurements were reliable. A significant difference (P < 0.05 for the four measurement parameters) was found at 50kHz between CTT and surrounding NTT. It was also found that Z and R of CTT were generally smaller than that of surrounding NTT. In conclusion, bioimpedance at a particular frequency is a potentially promising technique for tongue cancer screening.

Non-invasive and transdermal measurement of blood uric acid level in human by electroporation and reverse iontophoresis.

The aim of this study was to find out the optimum combination of electroporation (EP) and reverse iontophoresis (RI) on noninvasive and transdermal determination of blood uric acid level in humans. EP is the use of high-voltage electric pulse to create nano-channels on the stratum corneum, temporarily and reversibly. RI is the use of small current to facilitate both charged and uncharged molecule transportation across the skin. It is believed that the combination of these two techniques has additional benefits on the molecules’ extraction across the human skin. In vitro studies using porcine skin and diffusion cell have indicated that the optimum mode for transdermal uric acid extraction is the combination of RI with symmetrical biphasic direct current (current density = 0.3 mA/cm2; phase duration = 180 s) and EP with 10 pulses per second (voltage = 100 V/cm2; pulse width = 1 ms). This optimum mode was applied to six human subjects. Uric acid was successfully extracted through the subjects’ skin into the collection solution. A good correlation (r2 = 0.88) between the subject’s blood uric acid level and uric acid concentrations in collection solutions was observed. The results suggest that it may be possible to noninvasively and transdermally determine blood uric acid levels.

Simultaneous, noninvasive, and transdermal extraction of urea and homocysteine by reverse iontophoresis.

Background: Cardiovascular and kidney diseases are a global public health problem and impose a huge economic burden on health care services. Homocysteine, an amino acid, is associated with coronary heart disease, while urea is a harmful metabolic substance which can be used to reflect kidney function. Monitoring of these two substances is therefore very important. This in vitro study aimed to determine whether homocysteine is extractable transdermally and noninvasively, and whether homocysteine and urea can be extracted simultaneously by reverse iontophoresis. Methods: A diffusion cell incorporated with porcine skin was used for all experiments with the application of a direct current (dc) and four different symmetrical biphasic direct currents (SBdc) for 12 minutes via Ag/AgCl electrodes. The dc and the SBdc had a current density of 0.3 mA/cm2. Results: The SBdc has four different phase durations of 15 sec, 30 sec, 60 sec, and 180 sec. It was found that homocysteine can be transdermally extracted by reverse iontophoresis. Simultaneous extraction of homocysteine and urea by reverse iontophoresis is also possible. Conclusion: These results suggest that extraction of homocysteine and urea by SBdc are phase duration-dependent, and the optimum mode for simultaneous homocysteine and urea extraction is the SBdc with the phase duration of 60 sec.

A new approach for noninvasive transdermal determination of blood uric acid levels

The aims of this study were to investigate the most effective combination of physical forces from laser, electroporation, and reverse iontophoresis for noninvasive transdermal extraction of uric acid, and to develop a highly sensitive uric acid biosensor (UAB) for quantifying the uric acid extracted. It is believed that the combination of these physical forces has additional benefits for extraction of molecules other than uric acid from human skin. A diffusion cell with porcine skin was used to investigate the most effective combination of these physical forces. UABs coated with ZnO2 nanoparticles and constructed in an array configuration were developed in this study. The results showed that a combination of laser (0.7 W), electroporation (100 V/cm2), and reverse iontophoresis (0.5 mA/cm2) was the most effective and significantly enhanced transdermal extraction of uric acid. A custom-designed UAB coated with ZnO2 nanoparticles and constructed in a 1×3 array configuration (UAB-1×3-ZnO2) demonstrated enough sensitivity (9.4 μA/mM) for quantifying uric acid extracted by the combined physical forces of laser, electroporation, and RI. A good linear relationship (R2=0.894) was demonstrated to exist between the concentration of uric acid (0.2–0.8 mM) inside the diffusion cell and the current response of the UAB-1×3-ZnO2. In conclusion, a new approach to noninvasive transdermal extraction and quantification of uric acid has been established.

Portable urea biosensor based on the extended base bipolar junction transistor

In this study, an extended base bipolar junction transistor (EBBJT) was proposed to fabricate disposable urea biosensor. The detection of the urea is based on the variation of pH value. The gels, fabricated by the poly vinyl alcohol with pendent styrylpyridinium groups, were used to immobilize the urease. The SnO2/ITO glass, fabricated by sputtering SnO2 on the conductive ITO glass, was used as a pH-sensitive membrane for electrode, which is connected with a commercial bipolar junction transistor device. This readout circuit, fabricated in a 0.35-um CMOS 2P4M process, operated at 3.3V supply voltage. The circuit occupied an area of 1.0 mm × 0.9 mm. The dynamic range of the urea biosensor is from 1.4 to 64 mg/dl at the 10 mM phosphate buffer solution and the sensitivity of this range is about 65.8 mV/pUrea.

A creatinine biosensor based on admittance measurement

Regular check of blood creatinine level is very important as it is a measurement of renal function. Therefore, the objective of this study is to develop a simple and reliable creatinine biosensor based on admittance measurement for precise determination of creatinine. The creatinine biosensor was fabricated with creatinine deiminase immobilized on screen-printed carbon electrodes. Admittance measurement at a specific frequency ranges (22.80 - 84.71 Hz) showed that the biosensor has an excellent linear (r2 > 0.95) response range (50 - 250 uM), which covers the normal physiological and pathological ranges of blood creatinine levels. Intraclass correlation coefficient (ICC) showed that the biosensor has excellent reliability and validity (ICC = 0.98). In conclusion, a simple and reliable creatinine biosensor was developed and it is capable of precisely determining blood creatinine levels in both the normal physiological and pathological ranges.

Design and implementation of array readout integrated circuit and image system for current mode sensors

Considered that the dual band sensor system is the most popular design at present, this study discussed the design of a dual-band hybrid array readout circuit. The direct injection circuit structure was used in the unit pixel. The design, simulation, and layout were conducted in the 40um×40um unit pixel to complete middle and long waveband signal readouts, in order to achieve one sensor unit with two sensor modes. The readout circuit chip adopted TSMC 0.35um 2P4M CMOS 5V to design a 16×12 array readout circuit, with an input current range of the measured current at 1.9pA to 50 nA, an adjustable integration time, a maximum frame rate of 110Hz, the output swing of the chip signal of 2V, the maximum operating chip frequency of 3MHz, power dissipation of 18mW, system noise voltage Vrms of 0.68mV, and signal-noise ratio of 69dB. Finally, the tested chip was used to connect the detection system proxy board and digital signal board, and digital signal processing video through front-end filters and analog to digital converter, in order to complete signal conversion and digital signal processing. With the digital control signal provided by the signal board and signal capture, the back-end digital signal was processed and imaged on the screen. The readout circuit chip connected the signal proxy board for testing. The overall system resolution reached 10 bit.