Hann-Huei Tsai

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 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 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.

The application of capillary force to a cantilever as a sensor for molecular recognition

This paper reports on a sensing mechanism created by converting a change in solid–liquid interfacial tension due to molecular interactions into a change in capillary force loading for a cantilever sensor design. Compared with former cantilever sensor designs based on surface stress measurement, the proposed mechanism takes advantage of capillary force to effectively amplify the signal output of the sensor by several orders of magnitude. A complementary-metal-oxide-semiconductor-based cantilever sensor design validates the proposed sensing mechanism. Detection of Biotin-NeutrAvidin specific binding in picomolar sample concentrations was demonstrated for the application of biochemical assay.

ISFET-based pH sensor composed of a high transconductance CMOS chip and a disposable touch panel film as the sensing layer

This study presents a high performance ion-selective field-effect-transistor (ISFET) based pH sensor utilizing commercial touch panel film (TPF) as the sensing material. The coated ITO/SiO2/Nb2O5 multilayer on the TPF is ideal for measuring dissociated hydrogen ions. A high transconductance MOSFET chip composed of 10 parallel FETs is used to convert the effective pH value into the equivalent gate voltage. An on-film Ag/AgCl reference electrode is also produced on the sensing film to further enhance the sensing performance. The industrial roll-to-roll production process for TPF sensing film and the quick plug-in slot make the sensing layer suitable for disposable applications. The pH sensing results show that the TPF-based pH sensor exhibits good response for detecting solutions of the pH values in 3-13. The rapid time response (<; 10 s) and good stability (C. V. <; 2%) confirm the sensing performance of the developed pH sensor. Moreover, the sensor also shows low response to the interference ions of sodium and potassium in the solution. The developed pH sensor has shown its capabilities for rapid and low-cost pH detections.

A NEW GAS BIO-SENSOR IN THE STRUCTURE OF A MICRO-MACHINED CLAMPED-CLAMPED INERTIAL BEAM AND ITS READOUT CIRCUIT

This study presents a novel gas bio-sensor in the form of a micro-machined resonator and its readout circuit. The resonator has the structure of a clamped-clamped beam with thermal actuation and piezo-resistive sensing that supports a plate capable of being attached with test gas molecules to detect gas concentration. The purpose of this study is to design and fabricate the micro-scaled inertial beam with its readout circuit in a system-on-chip package. The circuit includes a driver, a front-end converter, a feed-trough reduction unit, a square-wave converter and a phase detector. In the process of signal reading, the sensor is first driven by a DDS module and power amplifier, and then sense the vibrations by piezo-resistivity. The piezo-resistivity is detected by a Wheatstone bridge circuits. The carried signal of modulation is processed by a Wheatstone bridge circuits. An instrumentation amplifier adjusts the gain to the appropriate amplitude. The circuit with reduction on feed-through noise increases the SNR. Square wave conversion circuit and PFD process the signal and the driver reference signal to detect phase difference. The data of phase difference is counted into a microcontroller dsPIC4011 and then the data being transmitted to the computer by RS232 to a USB adapter. Finally, the whole circuit is implemented by using TSMC 0.35 2P4M process and one-step postprocessing.© 2012 ASME

A novel gas sensor in the form of micro-machined resonator and its readout circuit

This study presents a novel gas sensor in the form of a micro-machined resonator and its readout circuit. The resonator has the structure of clamped-clamped beams with thermal actuation and piezo-resistive sensing that supports a plate capable of being attached with test gas molecules to detect gas concentration. The purpose of this study was to design a new gas sensor readout system for a clamped-clamped beam resonator with thermal actuation and piezo-resistive sensing and also presents a new approach to reject the feed-through noise. The sensor is driven by a DDS module and power amplifier, and then sense the vibrations by piezo-resistivity. The piezo-resistivity is detected by a Wheatstone bridge circuits. The carried signal of modulation is set in Wheatstone bridge circuits. An instrumentation amplifier adjusts the gain to the appropriate amplitude. The circuit with reduction on feed-through noise increases the SNR. Square wave conversion circuit and PFD process the signal and the driver reference signal to detect phase difference. The data of phase difference is counted into a microcontroller dsPIC4011 and then the data being transmitted to the computer by RS232 to a USB adapter. Finally, the whole circuit is implemented by using TSMC 0.35µm 2P4M process and one-step post-processing.