Pei-Ming Wu

Brain temperature measurement: A study of in vitro accuracy and stability of smart catheter temperature sensors

The injured brain is vulnerable to increases in temperature after severe head injury. Therefore, accurate and reliable measurement of brain temperature is important to optimize patient outcome. In this work, we have fabricated, optimized and characterized temperature sensors for use with a micromachined smart catheter for multimodal intracranial monitoring. Developed temperature sensors have resistance of 100.79u2009±u20091.19Ω and sensitivity of 67.95xa0mV/°C in the operating range from15–50°C, and time constant of 180xa0ms. Under the optimized excitation current of 500xa0μA, adequate signal-to-noise ratio was achieved without causing self-heating, and changes in immersion depth did not introduce clinically significant errors of measurements (<0.01°C). We evaluated the accuracy and long-term drift (5xa0days) of twenty temperature sensors in comparison to two types of commercial temperature probes (USB Reference Thermometer, NIST-traceable bulk probe with 0.05°C accuracy; and IT-21, type T type clinical microprobe with guaranteed 0.1°C accuracy) under controlled laboratory conditions. These in vitro experimental data showed that the temperature measurement performance of our sensors was accurate and reliable over the course of 5xa0days. The smart catheter temperature sensors provided accuracy and long-term stability comparable to those of commercial tissue-implantable microprobes, and therefore provide a means for temperature measurement in a microfabricated, multimodal cerebral monitoring device.

Micromachined lab-on-a-tube sensors for simultaneous brain temperature and cerebral blood flow measurements

This work describes the development of a micromachined lab-on-a-tube device for simultaneous measurement of brain temperature and regional cerebral blood flow. The device consists of two micromachined gold resistance temperature detectors with a 4-wire configuration. One is used as a temperature sensor and the other as a flow sensor. The temperature sensor operates with AC excitation current of 500xa0μA and updates its outputs at a rate of 5xa0Hz. The flow sensor employs a periodic heating and cooling technique under constant-temperature mode and updates its outputs at a rate of 0.1xa0Hz. The temperature sensor is also used to compensate for temperature changes during the heating period of the flow sensor to improve the accuracy of flow measurements. To prevent thermal and electronic crosstalk between the sensors, the temperature sensor is located outside the “thermal influence” region of the flow sensor and the sensors are separated into two different layers with a thin-film Copper shield. We evaluated the sensors for accuracy, crosstalk and long-term drift in human blood-stained cerebrospinal fluid. These in vitro experiments showed that simultaneous temperature and flow measurements with a single lab-on-a-tube device are accurate and reliable over the course of 5xa0days. It has a resolution of 0.013xa0°C and 0.18xa0ml/100xa0g/min; and achieves an accuracy of 0.1xa0°C and 5xa0ml/100xa0g/min for temperature and flow sensors respectively. The prototype device and techniques developed here establish a foundation for a multi-sensor lab-on-a-tube, enabling versatile multimodality monitoring applications.

Evaluation of microelectrode materials for direct-current electrocorticography.

OBJECTIVEnDirect-current electrocorticography (DC-ECoG) allows a more complete characterization of brain states and pathologies than traditional alternating-current recordings (AC-ECoG). However, reliable recording of DC signals is challenging because of electrode polarization-induced potential drift, particularly at low frequencies and for more conducting materials. Further challenges arise as electrode size decreases, since impedance is increased and the potential drift is augmented. While microelectrodes have been investigated for AC-ECoG recordings, little work has addressed microelectrode properties for DC-signal recording. In this paper, we investigated several common microelectrode materials used in biomedical application for DC-ECoG.nnnAPPROACHnFive of the most common materials including gold (Au), silver/silver chloride (Ag/AgCl), platinum (Pt), Iridium oxide (IrOx), and platinum-iridium oxide (Pt/IrOx) were investigated for electrode diameters of 300 μm. The critical characteristics such as polarization impedance, AC current-induced polarization, long-term stability and low-frequency noise were studied in vitro (0.9% saline). The two most promising materials, Pt and Pt/lrOx were further investigated in vivo by recording waves of spreading depolarization, one of the most important applications for DC-ECoG in clinical and basic science research.nnnMAIN RESULTSnOur experimental results indicate that IrOx-based microelectrodes, particularly with composite layers of nanostructures, are excellent in all of the common evaluation characteristics both in vitro and in vivo and are most suitable for multimodal monitoring applications. Pt electrodes suffer high current-induced polarization, but have acceptable long-term stability suitable for DC-ECoG. Major significance. The results of this study provide quantitative data on the electrical properties of microelectrodes with commonly-used materials and will be valuable for development of neural recordings inclusive of low frequencies.

Hot-Embossed Piezoelectric Polymer Micro-Diaphragm Arrays Integrated with Lab-on-a-Chip for Protein Analysis

Piezoelectric copolymer, PVDF-TrFE, diaphragm arrays with integrated microfluidic chip for high performance protein immunosensors were developed and characterized in this work. Mold-transfer and hot-embossing techniques provide a high throughput and repeatable way to fabricate piezoelectric polymer diaphragms and PVDF-TrFEs hydrophobic surface acts as a natural bioreceptor to capture proteins of interest. In addition, integrated microfluidic devices enhance reaction efficiency and reduce the assay time.

Cerebral blood flow sensor with in situ temperature and thermal conductivity compensation

A micromachined blood flow sensor with in situ tissue temperature and thermal conductivity compensation was developed for the continuous and quantitative measurement of intraparenchymal regional cerebral blood flow. The flow sensor operates in a constant-temperature mode and employs a periodic heating and cooling technique. Thermal conductivity compensation is realized by sampling the peak current outputs at the beginning of the heating period and the baseline temperature variation during the heating period is compensated by an integrated temperature sensor. This approach provides highly reliable data with MEMS-based thin film sensors. It achieves sensitivity of 1.467 mV/ml/100gram-min in the linear range from 0 to 160 ml/100gram-min.

Smart catheter flow sensor for continuous regional cerebral blood flow monitoring

This work reports on development of a novel smart catheter flow sensor (SCF) for continuous monitoring of regional cerebral blood flow (CBF). The SCF employs a periodic heating technique rather than continuous heating and calibrates itself every 5 seconds. This approach ensures zero drift for long-term continuous monitoring and can provide reliable data with MEMS-based thin film sensors. In addition, it uses a 4-wire configuration to eliminate lead wire effect and employs ratiometric measurement to deduce the resistance of SCF. Hence, it is more precise when compared to the bridge-type thermal diffusion flow sensor. The developed SCF has a sensitivity of 2.47mV/ml/min in the range from 0 to 100ml/min with a linear correlation coefficient of R2 = 0.9969. It achieves a resolution of 0.5ml/min and an accuracy better than 3ml/min of full scale with both temperature and medium thermal conductivity compensation.

Highly accurate thermal flow microsensor for continuous and quantitative measurement of cerebral blood flow.

Cerebral blood flow (CBF) plays a critical role in the exchange of nutrients and metabolites at the capillary level and is tightly regulated to meet the metabolic demands of the brain. After major brain injuries, CBF normally decreases and supporting the injured brain with adequate CBF is a mainstay of therapy after traumatic brain injury. Quantitative and localized measurement of CBF is therefore critically important for evaluation of treatment efficacy and also for understanding of cerebral pathophysiology. We present here an improved thermal flow microsensor and its operation which provides higher accuracy compared to existing devices. The flow microsensor consists of three components, two stacked-up thin film resistive elements serving as composite heater/temperature sensor and one remote resistive element for environmental temperature compensation. It operates in constant-temperature mode (~2xa0°C above the medium temperature) providing 20xa0ms temporal resolution. Compared to previous thermal flow microsensor based on self-heating and self-sensing design, the sensor presented provides at least two-fold improvement in accuracy in the range from 0 to 200xa0ml/100xa0g/min. This is mainly achieved by using the stacked-up structure, where the heating and sensing are separated to improve the temperature measurement accuracy by minimization of errors introduced by self-heating.

Development of a portable analyzer with polymer lab-on-a-chip (LOC) for continuous sampling and monitoring of Pb(II).

A new portable analyzer with polymer lab-on-a-chip (LOC) has been designed, fabricated and fully characterized for continuous sampling and monitoring of lead (Pb(II)) in this work. As the working electrodes of the sensor, bismuth (Bi (III)) which allowed the advantage of being more environmentally friendly than traditional mercury drop electrodes was used, while maintaining similar sensitivity and other desirable characteristics. The size of a portable analyzer was 30 cmx23 cmx7 cm, and the weight was around 3 kg. The small size gives the advantage of being portable for field use while not sacrificing portability for accuracy of measurement. Furthermore, the autonomous system developed in coordination with the development of new polymer LOC integrated with electrochemical sensors can provide an innovative way to monitor surface waters in an efficient, cost-effective and sustainable manner.

A novel biocompatible biomaterial for on-demand generation of three-dimensional oxygen gradients in vitro

Oxygen gradients play essential roles in many in vitro cell, tissue and organ experimental models. This paper reports a novel biocompatible biomaterial for on-demand generation of three-dimensional oxygen gradients in vitro. By exposing the oxygen-consuming biomaterial consisting of glucose oxidase and catalase enzymes to the cell culture media or gel, precisely-controlled oxygen gradients (2.5 mmHg per 100 μm distance) that closely mimic in vivo hypoxia can be generated. This biomaterial will serve as the basis for a new generation of experimental models previously impossible or very difficult to implement by simplifying and refining the control of in vitro microenvironments.

Multifunctional smart lab-on-a-tube (LOT) probe for monitoring traumatic brain injury (TBI)

A novel multifunctional smart lab-on-a-tube (LOT) is described to continuously and accurately monitor multiple physiological, metabolic and electrophysiological parameters that are vitally important in guiding the care of patients with traumatic brain injury. In addition to measuring various crucial parameters, the newly developed probe allows for drainage of excess cerebrospinal fluid as a strategy to reduce intracranial pressure.