Po-Hung Kuo

A Self-Powered CMOS Reconfigurable Multi-Sensor SoC for Biomedical Applications

A highly adaptive multi-sensor SoC comprising four on-chip sensors and a smart wireless acquisition system is first realized in standard CMOS process. To intelligently process different types (C/R/I/V) of sensor signals, a linear (R2 = 0.999) and reconfigurable sensor readout is proposed. A two-input energy harvesting interface with conversion efficiency of 73 % is also integrated for long-term use. Experimental results show that four physiological parameters (temperature, glucose/protein concentration, and pH value) can be simultaneously monitored using this chip.

A Passive Inertial Switch Using MWCNT–Hydrogel Composite With Wireless Interrogation Capability

This paper presents the development of a passive inertial switch using multiwall carbon nanotube (MWCNT)-hydrogel composite integrated with an inductor/capacitor (L -C) resonator. The device consists of a polydimethylsiloxane (PDMS) microfluidic chip containing MWCNT-hydrogel composite and water droplet and a glass substrate with a capacitor plate and an inductor coil. When the acceleration exceeds the designed threshold level, the water passes through the channel to the hydrogel cavity. The hydrogel swells and changes the capacitance of the integrated L-C resonator, which, in turn, changes the resonant frequency that can be remotely detected. Each sensor unit does not require onboard power and circuitry for operation, so the proposed device is disposable and is suitable for low-cost applications. All PDMS structures were fabricated using soft lithography. The L-C resonator was fabricated using a lift-off process to pattern metal layers on a glass substrate. The response time of the device is considerably reduced by introducing MWCNTs into the hydrogel composites. The dimensions of the device are 15 mm × 10 mm × 1.5 × mm. The characterization of the proposed device was also demonstrated. The threshold g-values, which differ for various applications, were strongly affected by the channel widths. The phase-dip measurement shows that the resonant frequencies shift from 164 to approximately 148 MHz when the device is activated by acceleration.

A Controlled-Release Drug Delivery System on a Chip Using Electrolysis

A system-on-a-chip (SOC) with integrated drug reservoirs for drug delivery is proposed. Electrolysis is used to generate microbubbles, which are employed as a force to open the reservoirs and release the drug. Wireless components, including an on/off keying receiver, microcontrol unit, regulator, clock divider, and power-on reset, are integrated for remote drug activation. The proposed microchip is fabricated by Taiwan Semiconductor Manufacturing Company 0.35-μm CMOS technology followed by post-IC processing. The total size is 2.48 mm2, and the power consumption is 7.57 mW. The in vitro experiment has proven the feasibility of the proposed drug delivery SOC.

A hydrogel-based implantable wireless CMOS glucose sensor SoC

An implantable wireless glucose monitoring SoC with hydrogel-based glucose sensor is proposed in CMOS 0.35 um technology. Owing to the reusable nature of the hydrogel glucose sensor and the wireless readout ability of the circuitry, this SoC is suitable for long-term and continuous monitoring. In-Vitro test shows a resolution of 40 mMole in glucose detection. The total power consumption of the SoC is 285 nW in standby mode and 11.9 mW in data transmission mode.

21.6 A smart CMOS assay SoC for rapid blood screening test of risk prediction

Rapid blood test is essential to disease control, risk assessment and point-of-care testing. Conventional enzyme-linked immunosorbent assay (ELISA) requires several hours or even days to get meaningful results. However, to some fierce contagious diseases, such as Ebola and SARS, the contagion can spread so fast that an instant and massive screening test is needed. A CMOS assay system-on-chip (SoC) offering a fast and cheap disease screening tool can be very helpful in the place where the medical resources are limited and the test is too costly to afford. Unlike the previously proposed CMOS biomolecular detection based on direct detection [1], a sandwiched assay detection protocol is adopted in this work, which possesses high sensitivity, high specificity and is free from pre-purified antigen process. As shown in Figure 1, a human blood sample containing the target biomolecules is applied on the proposed SoC. The test procedure includes blood filtration, biomolecular conjugation, electrolytic pumping, magnetic flushing and detection, automatically controlled by a micro-controller unit (MCU). The biomolecular signal is converted to the electrical signal by a CMOS-based Hall sensor array, as shown in the SEM image of Fig. 21.6.1, where the surface is coated with biomolecular probe. With the integration of the four LEDs and a battery, the detection steps can be indicated, providing an easy self-test point-of-care application.

A Smart CMOS Assay SoC for Rapid Blood Screening Test of Risk Prediction

A micro-controller unit (MCU) assisted immunoassay lab-on-a-chip is realized in 0.35 μm CMOS technology. The MCU automatically controls the detection procedure including blood filtration through a nonporous aluminum oxide membrane, bimolecular conjugation with antibodies attached to magnetic beads, electrolytic pumping, magnetic flushing and threshold detection based on Hall sensor array readout analysis. To verify the function of this chip, in-vitro Tumor necrosis factor- α (TNF- α) and N-terminal pro-brain natriuretic peptide (NT-proBNP) tests are performed by this 9 mm 2-sized single chip. The cost, efficiency and portability are considerably improved compared to the prior art.

A Remotely-Controlled Locomotive IC Driven by Electrolytic Bubbles and Wireless Powering

As implantable medical CMOS devices become a reality [1], motion control of such implantable devices has become the next challenge in the advanced integrated micro-system domain. With integrated sensors and a controllable propulsion mechanism, a micro-system will be able to perform tumor scan, drug delivery, neuron stimulation, bio-test, etc, in a revolutionary way and with minimum injury. Such devices are especially suitable for human hollow organs, such as urinary bladder and stomach. Motivated by the art reported in ISSCC 2012 [2], we demonstrate a remotely-controlled locomotive CMOS IC which is realized in TSMC 0.35μm technology. As illustrated in Fig. 18.7.1, a bare CMOS chip flipped on a liquid surface can be moved to the desired position without any wire connections. Instead of Lorentz forces [2], this chip utilizes the gas pressure resulting from electrolytic bubbles as the propulsive force. By appointing voltages to the on-chip electrolysis electrodes, one can decide the electrolysis location and thereby control the bubbles emissions as well as the direction of motion. With power management circuits, wireless receiver and micro-control unit (MCU), the received signal can be exploited as the movement control as well as wireless power. Experiments show a moving speed of 0.3mm/s of this chip. The total size is 21.2mm2 and the power consumption of the integrated circuits and the electrolysis electrodes are 125.4μW and 82μW, respectively.

Non-invasive Drosophila ECG recording by using eutectic gallium-indium alloy electrode: a feasible tool for future research on the molecular mechanisms involved in cardiac arrhythmia.

Background Drosophila heart tube is a feasible model for cardiac physiological research. However, obtaining Drosophila electrocardiograms (ECGs) is difficult, due to the weak signals and limited contact area to apply electrodes. This paper presents a non-invasive Gallium-Indium (GaIn) based recording system for Drosophila ECG measurement, providing the heart rate and heartbeat features to be observed. This novel, high-signal-quality system prolongs the recording time of insect ECGs, and provides a feasible platform for research on the molecular mechanisms involved in cardiovascular diseases. Methods In this study, two types of electrode, tungsten needle probes and GaIn electrodes, were used respectively to noiselessly conduct invasive and noninvasive ECG recordings of Drosophila. To further analyze electrode properties, circuit models were established and simulated. By using electromagnetic shielded heart signal acquiring system, consisted of analog amplification and digital filtering, the ECG signals of three phenotypes that have different heart functions were recorded without dissection. Results and Discussion The ECG waveforms of different phenotypes of Drosophila recorded invasively and repeatedly with n value (n>5) performed obvious difference in heart rate. In long period ECG recordings, non-invasive method implemented by GaIn electrodes acts relatively stable in both amplitude and period. To analyze GaIn electrode, the correctness of GaIn electrode model established by this paper was validated, presenting accuracy, stability, and reliability. Conclusions Noninvasive ECG recording by GaIn electrodes was presented for recording Drosophila pupae ECG signals within a limited contact area and signal strength. Thus, the observation of ECG changes in normal and SERCA-depleted Drosophila over an extended period is feasible. This method prolongs insect survival time while conserving major ECG features, and provides a platform for electrophysiological signal research on the molecular mechanism involved in cardiac arrhythmia, as well as research related to drug screening and development.

A capacitive immunosensor using on-chip electrolytic pumping and magnetic washing techniques for point-of-care applications

This work presents a capacitive immunosensor using on-chip electrolytic pumping and magnetic washing techniques. The proposed device possesses the advantages such as simple operation, low power consumption, and portability. The proposed device was fabricated using typical micromachining process, and is suitable for mass-production. We also demonstrated the detection of N-Terminal pro-brain-Type natriuretic peptide (NT-proBNP) using the fabricated device integrated with a CMOS capacitance sensing chip. The proposed device potentially can be used as a portable system for point-of-care applications.

A 0.45-V Low-Power OOK/FSK RF Receiver in 0.18

A 0.45-V low-power 0.18 μm CMOS OOK/FSK RF receiver for implantable medical applications is proposed. The receiver utilizes a wake-up mechanism to adjust its power consumption automatically by reading the amplitude of the input wireless OOK/FSK modulated RF signal directly. No additional wireless wake-up commands are required. Such a normally-off and instanton scheme reduces the power consumption of this receiver significantly. The power consumption is 129 μW in sleep mode and 352 μW in wake-up mode. Other techniques, such as third-orderharmonic cancellation, subharmonic mixing, and forward body biasing are also adopted for better linearity, higher LO-to-RF isolation, and lower VDD, respectively. The measurement results show that the proposed receiver consumes only 2.6 nJ/bit (OOK) and 1 nJ/bit (FSK) to achieve the sensitivities of -55 dBm (OOK) and -53.5 dBm (FSK) in BER <; 10-3 constraint. The proposed receiver is designed for low-power and short-distance MICS band applications.