Yu-Jie Huang

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 CMOS wireless biomolecular sensing system-on-chip based on polysilicon nanowire technology

As developments of modern societies, an on-field and personalized diagnosis has become important for disease prevention and proper treatment. To address this need, in this work, a polysilicon nanowire (poly-Si NW) based biosensor system-on-chip (bio-SSoC) is designed and fabricated by a 0.35 μm 2-Poly-4-Metal (2P4M) complementary metal-oxide-semiconductor (CMOS) process provided by a commercialized semiconductor foundry. Because of the advantages of CMOS system-on-chip (SoC) technologies, the poly-Si NW biosensor is integrated with a chopper differential-difference amplifier (DDA) based analog-front-end (AFE), a successive approximation analog-to-digital converter (SAR ADC), and a microcontroller to have better sensing capabilities than a traditional Si NW discrete measuring system. In addition, an on-off key (OOK) wireless transceiver is also integrated to form a wireless bio-SSoC technology. This is pioneering work to harness the momentum of CMOS integrated technology into emerging bio-diagnosis technologies. This integrated technology is experimentally examined to have a label-free and low-concentration biomolecular detection for both Hepatitis B Virus DNA (10 fM) and cardiac troponin I protein (3.2 pM). Based on this work, the implemented wireless bio-SSoC has demonstrated a good biomolecular sensing characteristic and a potential for low-cost and mobile applications. As a consequence, this developed technology can be a promising candidate for on-field and personalized applications in biomedical diagnosis.

A release-on-demand wireless CMOS drug delivery SoC based on electrothermal activation technique

Recently, micro- and nano-technologies have enabled rapid progress in biomedical applications. Although in vitro analytical and diagnostic tools have been the focus of such technologies, in vivo therapeutic and sensing applications have received significant attention in the past few years. Novel implantable drug delivery devices, which can precisely control key therapy parameters, have the potential to increase the efficacy of drug therapy [1]. This paper presents an implantable CMOS drug delivery SoC, in which a wireless controller/actuation circuitry and a drug delivery array are monolithically integrated. Compared with current technologies, the advantages of the proposed device include lower system cost, smaller device size and lower power consumption. This device can be implanted by minimally invasive surgery and is suitable for the localized diagnosis/therapy of cancers, or the immediate treatment of unpredictable heart attacks [2] by releasing drugs such as nonapeptide leuprolide acetate or nitroglycerin. Physicians can also make non-invasive therapy modification by using the wireless capability.

A CMOS Cantilever-Based Label-Free DNA SoC With Improved Sensitivity for Hepatitis B Virus Detection

This paper presents a highly-integrated DNA detection SoC, where several kinds of cantilever DNA sensors, a readout circuit, an MCU, voltage regulators, and a wireless transceiver, are integrated monolithically in a 0.35 μm CMOS Bio-MEMS process. The cantilever-based biosensors with embedded piezoresistors aim to transduce DNA hybridization into resistance variation without cumbersome labeling process. To improve detection sensitivity for low DNA concentration use, an oscillator-based self-calibrated readout circuit with high precision is proposed to convert small resistance variation ( of original resistance) of the sensor into adequate frequency variation and further into digital data. Moreover, its wireless capacity enables isolation of the sample solution from electrical wire lines and facilitates data transmission. To demonstrate the effectiveness of full system, it is applied to detect hepatitis B virus (HBV) DNA. The experimental results show that it has the capability to distinguish between one base-pair (1-bp) mismatch DNAs and match DNAs and achieves a limit of detection (LOD) of less than 1 pM.

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 fully integrated hepatitis B virus DNA detection SoC based on monolithic polysilicon nanowire CMOS process

Polysilicon nanowire (poly-Si NW) based biosensor is integrated with the wireless acquisition circuits in a standard CMOS SoC for the first time. To improve detection quality, a chopper DDA-based analog front-end with features of low noise, high CMRR, and rail-to-rail input range is implemented. Additional temperature sensor is also included to compensate temperature drift of the biosensor. The results indicate that the detection limit is as low as 10fM. The capability to distinguish one base-pair mismatched DNAs is also demonstrated.

A Fully Integrated Humidity Sensor System-on-Chip Fabricated by Micro-Stamping Technology

A fully integrated humidity sensor chip was designed, implemented, and tested. Utilizing the micro-stamping technology, the pseudo-3D sensor system-on-chip (SSoC) architecture can be implemented by stacking sensing materials directly on the top of a CMOS-fabricated chip. The fabricated sensor system-on-chip (2.28 mm × 2.48 mm) integrated a humidity sensor, an interface circuit, a digital controller, and an On-Off Keying (OOK) wireless transceiver. With low power consumption, i.e., 750 μW without RF operation, the sensitivity of developed sensor chip was experimentally verified in the relative humidity (RH) range from 32% to 60%. The response time of the chip was also experimentally verified to be within 5 seconds from RH 36% to RH 64%. As a consequence, the implemented humidity SSoC paves the way toward the an ultra-small sensor system for various applications.

Identification of intertypic recombinant infectious bronchitis viruses from slaughtered chickens

ABSTRACT Avian coronavirus infectious bronchitis virus (IBV) poses a major threat to the global poultry industry. New IBV geno- and serotypes are continually reported. However, information on IBV prevalence is not frequently addressed in these reports. This study reports on a viral surveillance program in Taiwan from 2005 to 2006 with sampling conducted in poultry slaughterhouses. The genetic features of the obtained field isolates were investigated using sequence analysis and SimPlot analysis. A 1-directional neutralization test was performed to examine the antigenic variations among the collected viruses. The selection pressures that may contribute to the evolution of Taiwan IBV during recent decades were assessed. The surveillance program revealed that 8 out of 47 flocks (17%) were IBV-infected, from which 13 IBV isolates were recovered. Based on the phylogenetic analysis of the S1 gene, 11 of 13 isolates (84.6%) clustered with Taiwan group I. One IBV isolate showed evidence of frequent recombination events with China-like IBV in the spike glycoprotein (S) gene. Another isolate demonstrated the incorporation of China-like and H120-like genome fragments within the S2 gene and the membrane protein (M) gene region, respectively. Some antigenic changes were found in the 1-directional neutralization test. However, no positive selection pressures were related to those variations in the S1 genes among Taiwan IBV. Based on our work, we suggest that sampling chickens in poultry slaughterhouses is an effective and valuable means of compiling viral prevalence data, particularly in situations where there is subclinical infection. Infectious bronchitis viruses from slaughtered chickens revealed intertypic genetic recombination and antigenic diversity.

Analysis and design of on-sensor ECG processors for realtime detection of VF, VT, and PVC

Cardiovascular disease remains the main cause of death, and great efforts are spent on the design of ECG body sensors these years. Essential components such as analog frontend and wireless transceivers have been integrated on a compact IC with micro-Watt power consumption. To provide timely warning against the fatal vascular signs, based on the Chaotic Phase Space Differential (CPSD) algorithm, on-sensor processors are implemented to detect the abnormal ECG for VF, VT and PVC. The on-sensor processing reduces 98.0% power of wireless data transmission for raw ECG signals. The application specific processor is designed to accelerate CPSD algorithm with 1.7μW power while the OpenRISC is integrated to provide the system flexibility. The architecture is realized on the FPGA platform to physically demonstrate the detection of the abnormal ECG signals in a real time.

Analysis and Design of On-sensor ECG Processors for Realtime Detection of Cardiac Anomalies Including VF, VT, and PVC

Cardiovascular disease remains the main cause of death, and great efforts are spent on the design of ECG (electrocardiogram) body sensors these years. Essential components such as analog frontend and wireless transceivers have been integrated on a compact IC with micro-Watt power consumption. To provide timely warning against the fatal vascular signs, based on the Chaotic Phase Space Differential (CPSD) algorithm, heterogeneous VLSI processors are implemented and integrated to extract the abnormal ECG characteristics for VF (Ventricular Fibrillation), VT (Ventricular Tachycardia) and PVC (Premature Ventricular Contraction). The on-sensor processing reduces 98.0% power of wireless data transmission for raw ECG signals. The application specific processor is designed to accelerate CPSD algorithm with 1.7μW power while the OpenRISC is integrated to provide the system flexibility. The architecture is realized on the FPGA platform to demonstrate the detection of the abnormal ECG signals in realtime.