Sukhwan Choi

One-chip electronic detection of DNA hybridization using precision impedance-based CMOS array sensor

This paper describes a label-free and fully electronic detection method of DNA hybridization, which is achieved through the use of a 16×8 microarray sensor in conjunction with a new type of impedance spectroscopy constructed with standard complementary metal-oxide-semiconductor (CMOS) technology. The impedance-based method is based on changes in the reactive capacitance and the charge-transfer resistance after hybridization with complementary DNA targets. In previously published label-free techniques, the measured capacitance presented unstable capacitive properties due to the parallel resistance that is not infinite and can cause a leakage by discharging the charge on the capacitor. This paper presents an impedance extraction method that uses excitation by triangular wave voltage, which enables a reliable measurement of both C and R producing a highly sensitive sensor with a stable operation independent of external variables. The system was fabricated in an industrial 0.35-μm 4-metal 2-poly CMOS process, integrating working electrodes and readout electronics into one chip. The integrated readout, which uses a parasitic insensitive integrator, achieves an enlarged detection range and improved noise performance. The maximum average relative variations of C and R are 31.5% and 68.6%, respectively, after hybridization with a 1 μM target DNA. The proposed sensor allows quantitative evaluation of the molecule densities on the chip with distinguishable variation in the impedance. This fully electronic microsystem has great potential for use with bioanalytical tools and point-of-care diagnosis.

23.5 An energy pile-up resonance circuit extracting maximum 422% energy from piezoelectric material in a dual-source energy-harvesting interface

Energy harvesting is one of the key technologies used to realize self-sustaining systems such as wireless sensor networks and health-care devices. Much research on circuit design has been conducted to extract as much energy as possible from transducers, such as the thermoelectric generator (TEG) and the piezoelectric transducer (PZT). Specifically, the energy in a PZT could be extracted more efficiently by utilizing resonance as [1] and [2] demonstrated. However, the maximum output voltage swing in those techniques are limited to twice of the original swing of the PZT, and thus, had a limited energy extraction capability in spite of more energy being available from the PZT. In [3], on the other hand, the large energy is obtained with higher voltage swing, but is limited up to 247% because the load energy is used to increase the output voltage swing of PZT. To obtain far more power from PZT, we propose an alternative resonance technique through which the PZT output swing can be boosted as high as CMOS devices can sustain. This technique is applied to a dual-energy-sourced (PZT and TEG) energy-harvesting interface (EHI) as a battery charger.

A CMOS label-free DNA sensor using electrostatic induction of molecular charges.

This paper reports a label-free biosensor for the detection of DNA hybridization. The proposed biosensor measures the surface potential on oligonucleotide modified electrodes using a direct charge accumulation method. The sensor directly and repeatedly measures the charges induced in the working electrode, which correspond to intrinsic negative charges in immobilized molecules. The sensor achieves an improved signal-to-noise ratio (SNR), through the oversampling effect of accumulation for charges and the differential architecture. The sensor also shows stable, robust, and reproducible measurement independent of slight changes in the reference voltage, unlike previous ion-sensitive field effect transistors (ISFETs), providing the benefits of choosing a wide variety of reference electrode materials. The proposed device is integrated with working electrodes, a reference electrode and readout circuits into one package via a 0.35 μm complementary metal-oxide-semiconductor (CMOS) process. The sensor achieves a detectable range of 88.3 dB and a detection limit of 36 μV for surface potential. It is demonstrated that the sensor successfully achieves specific detection of oligonucleotide sequences derived from the H5N1 avian influenza virus. The experiments show a limit of detection of 100 pM and include a single-base mismatch test in 18-mer oligonucleotides.

CMOS capacitive biosensor with enhanced sensitivity for label-free DNA detection

Silicon devices based on impedance measurements offer label-free and direct electrical detection when used to quantify the hybridization of DNA molecules. They show rapid, robust, and inexpensive measurement and compatibility with commercial microfabrication technology. The real-time measurement of the impedance does not require the use of labeling molecules attached to the target DNA in optical and magnetic technology [1,2]. It also has the advantage of miniaturization for point-of-care (PoC) or on-site sensing applications, unlike the 3-electrode topology in electrochemical sensors [3]. Several studies have proposed capacitive biosensors that utilize a nonfaradaic process, which refers to transient currents charging a geometrical capacitor in an electrolyte-electrode interface [4]. Conventional capacitive biosensors using the excitation of the bidirectional current [5,6] can be implemented with a compact design, but they have several issues that degrade the sensitivity of the sensor, such as DC drift in the electrode caused by a charge imbalance, the electrolysis generated by DC voltage across the electrodes, the offset generated by pre-charged initial values, and weakness against common-mode noise. As a solution, we report a fully integrated capacitance-based biosensor that locates two electrodes differentially in a single current source.

A CMOS impedance cytometer for 3D flowing single-cell real-time analysis with ΔΣ error correction

Flow cytometry is an essential cell analysis technology in clinical immunology and haematology for the diagnosis and prognosis of disease. It involves the counting, identification and sorting of cells [1,2]. Conventional bulk measurements [3] require a large volume of blood, which is not desirable for the early detection of a disease, when only a very small percentage of cells contain evidence of the disease. In this paper, we propose, for the first time, a non-invasive and high-throughput single-cell analysis method using CMOS-integrated circuits in conjunction with a microfluidic channel as the first building block of a complete cell-sorting device.

PSR Enhancement Through Super Gain Boosting and Differential Feed-Forward Noise Cancellation in a 65-nm CMOS LDO Regulator

This paper presents a 65-nm CMOS low-dropout (LDO) regulator employing a super gain amplifier (SGA) and differential feed-forward noise cancellation to maximize the power supply rejection (PSR). The SGA in the error amplifier is augmented by a positive feedback current mirror, and this SGA boosts the loop gain through local negative feedback. With 1.2 V supply voltage, the LDO regulator has a 200 mV drop-out voltage and the ability to handle a maximum 25 mA load current. The measurement results show a -47 dB PSR ratio of up to 10 MHz and dc load regulation under 1 mV for full load current change.

An autonomous CMOS hysteretic sensor for the detection of desorption-free DNA hybridization

This paper describes a sensor for label-free, fully electrical detection of DNA hybridization based on capacitive changes in the electrode-electrolyte interface. The sensor measures capacitive changes in real time according to a charging-discharging principle that is limited by the hysteresis window. In addition, a novel autonomous searching technique, which exclusively monitors desorption-free hybridized electrodes among electrode arrays, enhances the performance of the sensor compared with conventional capacitive measurement. The sensor system achieves a detection range of 80 dB. The integrated circuit sensor is fabricated with a 0.35 μm CMOS process. The proposed sensor offers rapid, robust and inexpensive measurement of capacitance with highly integrated detection circuitry. It also facilitates quantitative evaluations of molecular densities on a chip with distinctive impedance variations by monitoring desorption-free hybridized electrodes. Our electrical biosensor has great potential for use with bio analytical tools and point-of-care diagnosis.

An electronic DNA sensor chip using integrated capacitive read-out circuit

This paper presents fully integrated label-free DNA recognition circuit based on capacitance measurement. A CMOS-based DNA sensor is implemented for the electrical detection of DNA hybridization. The proposed architecture detects the difference of capacitance through the integration of current mismatch of capacitance between reference electrodes functionalized with only single-stranded DNA and sensing electrodes bound with complementary DNA strands specifically. In addition, to minimize the effects of parallel resistance between electrodes and DNA layers, the compensation technique of leakage current through the use of constant current charging and discharging is implemented in the proposed detection circuit. The chip was fabricated in 0.35um 4-metal 2-poly CMOS process, and 16×8 sensing electrode arrays were fabricated by post-processing steps.

Auto-Scaling Overdrive Method Using Adaptive Charge Amplification for PRAM Write Performance Enhancement

A PRAM write driver with an auto-scaling overdrive method is presented. The proposed overdrive method significantly reduces the rise time of the cell-current pulse for bit-line parasitic components of 3 pF and 6 k Ω, and it lowers the complexity of the overdrive control using an adaptive charge amplification technique. A rise time of less than 15 ns is achieved and shortened up to 4.7 times, and the total write-throughput is increased. The rise time is reduced consistently for all levels of the target-current by the auto-scaling effect. Therefore, cell heating control becomes more linear in program-and-verify (PNV) operation. Due to its simple adding-on structure, it is easily compatible with a conventional write driver. A prototype chip was implemented using a 0.18- μm CMOS process. It is also applicable to smaller-scale technology.

An 83% peak efficiency and 1.07W/mm 2 power density Single Inductor 4-Output DC-DC converter with Bang-Bang Zero th -Order Control

This paper presents a new control scheme dubbed Bang-Bang Zeroth-Order Control (BBZOC) for Single Inductor Multiple Output (SIMO) buck converter. The main loop control utilizes a phase detector, charge pump, filter, and comparator. The SIMO buck converter with BBZOC simplifies the compensation design compared to conventional voltage mode control. This work is fabricated in 1P4M 0.35um BCD process and achieves 83% maximum efficiency with the rated output power of 1.04W. The maximum output power is 2.7W and the maximum power density is 1.07 W/mm2. Considering the difference in the process, this work represents the state of the art in the power density.