A highly adaptive multi-sensor SoC comprising four integrated on-chip sensors and a smart wireless acquisition system is realized in standard CMOS process for the first time. To intelligently process different types (C, R, I, and V) of sensor signals, a linear (R-square is 0.999) and reconfigurable sensor readout is proposed based on switched-capacitor circuit technology. In addition, a dual-input energy harvesting interface with conversion efficiency of 73% is also integrated to pick up light energy and RF power, which potentiates long-term use without battery replacement. The entire SoC occupies die area of 11.25 mm 2 and consumes only 942.9 μW. Experimental results show that four physiological parameters (temperature, glucose and protein concentration, and pH value) can be simultaneously monitored using this chip. This system can be seen as a universal sensor platform. Different types of sensors can be easily integrated into it for convenient use, which dramatically reduces time consuming of building a new sensor system.

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

This paper demonstrates a numerical modeling of surface plasmon resonance (SPR) biosensor for detecting DNA hybridization by recording the resonance frequency characteristics (RFC). The proposed sensor is designed based on graphene material as biomolecular recognition elements (BRE) and the sharp SPR curve of gold (Au). Numerical analysis shows that the variation of RFC for mismatched DNA strands is quiet negligible whereas that for complementary DNA strands is considerably countable. Here, graphene is used to perform faster immobilization between target DNA and probe DNA. The usage of graphene also changes the RFC that ensure hybridization of DNA event by utilizing its optochemical property. In addition, proposed sensor successfully distinguishes between hybridization and single-nucleotide polymorphisms (SNP) by observing the variation level of RFC and maximum transmittance. Therefore, the proposed frequency readout based SPR sensor could potentially open a new window of detection for biomolecular interactions. We also highlight the advantage of using graphene sublayer by performing the sensitivity analysis. Sandwiching of each graphene sublayer enhances 95% sensitivity comparing with conventional SPR sensor.

/pdf/dna-hybridization-detection-based-on-resonance-frequency-3dgaff7z11.pdf

DNA Hybridization Detection Based on Resonance Frequency Readout in Graphene on Au SPR Biosensor

 Abstract—The fast development of micro-electromechanical system (MEMS) technology has brought many great ideas in the field of biomedical applications. A biosensor is a chemical sensing device in which a biologically derived recognition analyte coupled to a transducer to allow the quantitative development of biochemical parameter. A biosensor consists of a bio-element and a sensor-element. The bio-element may be an enzyme, antibody, living cells, tissue, etc., and the sensing element may be electric current, electric potential, and so on and specificity of analyte is the important concept in biosensor. In this paper we review the principle of microcantilever, biosensing mechanism and applications of microcantilevers for bio detection for early detection of diseases accurately. Biosensors can have a variety of biomedical, industry, and military applications. The main advantages of MEMS based sensors are specificity, portability, simplicity, high sensitivity, potential ability for real-time and on-site analysis coupled with the high speed and low cost.

/pdf/microcantilever-based-biosensor-for-disease-detection-fvc9hq6ic6.pdf

Microcantilever based Biosensor for Disease Detection Applications

Complementary metal oxide semiconductor (CMOS) technology enables low-cost and large-scale integration of transistors and physical sensing materials on tiny chips (e.g., <1 cm2), seamlessly combining the two key functions of biosensors: transducing and signal processing. Recent CMOS biosensors unified different transducing mechanisms (impedance, fluorescence, and nuclear spin) and readout electronics have demonstrated competitive sensitivity for in vitro diagnosis, such as detection of DNA (down to 10 aM), protein (down to 10 fM), or bacteria/cells (single cell). Herein, we detail the recent advances in CMOS biosensors, centering on their key principles, requisites, and applications. Together, these may contribute to the advancement of our healthcare system, which should be decentralized by broadly utilizing point-of-care diagnostic tools.

/pdf/cmos-biosensors-for-in-vitro-diagnosis-transducing-14oa3otoks.pdf

CMOS biosensors for in vitro diagnosis – transducing mechanisms and applications

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

This paper presents a 1-V and low-noise readout front-end for biomedical applications. The key to this low-voltage and low-power operation is the current-mode instrumentation amplifier (CMIA). To reject the DC offset, an active-RC integrator with the subthreshold-biased PMOS as high resistance is included in the CMIA and forms the offset cancellation loop. The nested-chopper technique is applied to reduce the flicker noise and improve the common-mode rejection ratio (CMRR). A proposed third-order G m -C low-pass filter (LPF) is incorporated to remove the modulated noise by the choppers. Furthermore, a digitally programmable gain stage is incorporated to provide adjustable gain range for the readout front-end. The overall readout front-end has a bandwidth of 140 Hz and achieves 125-dB CMRR, 90-dB power-supply rejection ratio (PSRR), and 6-nV/rtHz input-referred noise density. The readout front-end is fabricated in a 0.18-µm CMOS process. Total power consumption is 182 µW from a 1-V supply.

A 1-V low-noise readout front-end for biomedical applications in 0.18-µm CMOS

A highly-integrated DNA detection SoC, which includes DNA sensors, readout circuit, MCU, and OOK TX/RX, is implemented in a 0.35µm CMOS Bio-MEMS process. For low DNA concentration, an oscillator-based self-calibrated readout circuit with high sensitivity (2kHz/Ω) is proposed to convert small resistance variation of the piezoresistive cantilever sensor into adequate frequency shift. The measured results reveal that it could detect &#60;0.02% of resistance variation (0.6Ω) and cover detection concentration range of specific DNA from 100pM to 1µM.

http://ieeexplore.ieee.org/iel5/5976946/5985982/05986419.pdf

A fully-integrated cantilever-based DNA detection SoC in a CMOS Bio-MEMS process

An integrated DNA detection system-on-chip (SoC), which includes microcantilever based DNA sensors, readout circuits, MCU, and RF OOK TX/RX, is implemented by a 0.35µm CMOS Bio-MEMS process and post-processing steps. For DNA sensing, the DNA immobilization process is used to make the probe DNA attaches on the surface of microcantilever via sulfur-gold covalent bond. Then the biosensor is proved to be sensitive to surface stress change induced by DNA hybridization on the surface of the microcantilever. The experiment results reveal the developed DNA detection SoC has excellent selectivity and detection concentration range of the specific DNA from 1pM to 10nM.

/pdf/an-integrated-microcantilever-based-wireless-dna-chip-for-4c72d0b8rs.pdf

Bing-Jye Kuo

Papers

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

A 1-V low-noise readout front-end for biomedical applications in 0.18-µm CMOS

A fully-integrated cantilever-based DNA detection SoC in a CMOS Bio-MEMS process

An integrated microcantilever-based wireless dna chip for hepatitis b virus (hbv) dna detection