Zhizhen Wu

Single probe for real-time simultaneous monitoring of neurochemistry and direct-current electrocorticography.

We report a novel single neural probe for real-time simultaneous monitoring of multiple neurochemicals and direct-current electrocorticography (DC-ECoG). A major advance of this probe is the inclusion of two iridium oxide reference electrodes to improve sensor accuracy. The ECoG reference electrode is identical to the ECoG recording electrodes to significantly improve DC stability, while the reference for electrochemical sensors has 10-fold lower polarization rate to minimize the small current-induced drift in the reference electrode potential. In vitro, the single probe selectively measured oxygen (r(2)=0.985 ± 0.01, concentration range=0-60 mmHg, limit of detection=0.4 ± 0.07 mmHg) and glucose (r(2)=0.989 ± 0.009, concentration range=0-4mM, limit of detection=31 ± 8 µM) in a linear fashion. The performance of the single probe was assessed in an in vivo needle prick model to mimic sequelae of traumatic brain injury. It successfully monitored the theoretically expected transient brain oxygen, glucose, and DC potential changes during the passage of spreading depolarization (SD) waves. We envision that the developed probe can be used to decipher the cause-effect relationships between multiple variables of brain pathophysiology with the high temporal and spatial resolutions that it provides.

Smart catheter flow sensor for real-time continuous regional cerebral blood flow monitoring

We present a smart catheter flow sensor for real-time, continuous, and quantitative measurement of regional cerebral blood flow using in situ temperature and thermal conductivity compensation. The flow sensor operates in a constant-temperature mode and employs a periodic heating and cooling technique. This approach ensures zero drift and provides highly reliable data with microelectromechanical system-based thin film sensors. The developed flow sensor has a sensitivity of 0.973 mV/ml/100 g/min in the range from 0 to 160 ml/100 g/min with a linear correlation coefficient of R2 = 0.9953. It achieves a resolution of 0.25 ml/100 g/min and an accuracy better than 5 ml/100 g/min.

Evaluation of microelectrode materials for direct-current electrocorticography.

OBJECTIVE Direct-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. APPROACH Five 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. MAIN RESULTS Our 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.

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.

Polysilicon Thin Film Developed on Flexible Polyimide for Biomedical Applications

Flexible pressure and thermal sensors are the critical parts of the functional electronic skin of prostheses and robots, as well as flexible catheter/devices for multimodal biomedical monitoring. In this paper, a polysilicon thin film was developed on a flexible polyimide substrate using aluminum induced crystallization process for biomedical pressure and temperature sensing applications. The formation of polycrystalline structure was verified from the developed polysilicon film. Long term stability and real-time temperature tests were performed to evaluate potential application to the in vivo monitoring of brain or body temperature. The linear real-time change of polysilicon resistance with temperature was attained with the temperature coefficient of the resistance of -0.0027/°C and the resolution of 0.05 °C. With a gauge factor of 10.3, the polysilicon film developed in this paper represents a promising material for the development of high-sensitivity pressure sensors on flexible polyimide substrates.

A wearable pressure and temperature sensor array using polysilicon thin film on polyimide

This paper reports a high sensitive flexible and wearable pressure and temperature sensor array with polysilicon thin film (PTF). PTF was developed on flexible polyimide with aluminum induced crystallization at low temperature and used as the sensing material for both pressure and temperature sensors. The developed pressure sensor has high sensitivity of 1.01 mV/ kPa and resolution of 100 Pa, and temperature sensor has high sensitivity of 2.26 mV/ °C and resolution of 0.1 °C. The pressure and temperature sensor array with high sensitivity, resolution and low cross talk can be very applicable for the electronic skin of robotic fingers, prostheses and biomedical monitoring.

Polysilicon based flexible temperature sensor for high spatial resolution brain temperature monitoring

In this paper, we present a flexible temperature sensor with ultra-small polysilicon thermistors for brain temperature monitoring. In vitro sensitivity, resolution, thermal hysteresis and long term stability tests were performed. Temperature coefficient of resistance (TCR) of -0.0031/ °C and resolution of 0.1 °C were obtained for the sensor. Thermal hysteresis for temperature range of 30~45 °C was less than 0.1 °C. With silicon nitride as the passivation layer, the temperature sensor showed a drift within 0.3 °C for 3 days long term stability test in water. In vivo tests showed a clear correlation between the localized brain temperature and electrocorticography (ECoG) signal during spreading depolarization. The developed flexible temperature sensor with small size polysilicon thermistors can be adopted for high resolution brain temperature mapping as well as multimodal monitoring with limited sensing space.

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.

Brain-friendly amperometric enzyme biosensor based on encapsulated oxygen generating biomaterial

A novel first-generation Clark-type biosensor platform that can eliminate the oxygen dependence has been presented. Sufficient oxygen to drive the enzymatic reaction under hypoxic conditions was produced by encapsulated oxygen generating biomaterial, calcium peroxide. The catalase immobilized in chitosan matrix was coated on top of the groove to decompose residual hydrogen peroxide to oxygen. A glucose biosensor was developed on the proposed platform as proof of concept. Under hypoxic conditions, developed glucose biosensors maintained their sensitivity response around 84% of their response at oxygen tension of 151mmHg. The sensitivity deviation was less than 5.3% with the oxygen tension traversed from 0 to 57 mmHg. Under oxygen tension of 8.3mmHg, the sensitivity of 37.130nA/mM and the linear coefficient of R2=0.9968 were obtained with the glucose concentration varying from 0.05 to 10mM. This new platform is particularly attractive for injured brain monitoring.