Real-time label-free quantitative monitoring of biomolecules without surface binding by floating-gate complementary metal-oxide semiconductor sensor array integrated with readout circuitry (original) (raw)

Labelfree fully electronic nucleic acid detection system based on a field-effect transistor device

Biosensors and Bioelectronics, 2004

The labelfree detection of nucleic acid sequences is one of the modern attempts to develop quick, cheap and miniaturised hand-held devices for the future genetic testing in biotechnology and medical diagnostics. We present an approach to detect the hybridisation of DNA sequences using electrolyte-oxide-semiconductor field-effect transistors (EOSFETs) with micrometer dimensions. These semiconductor devices are sensitive to electrical charge variations that occur at the surface/electrolyte interface, i.e. upon hybridisation of oligonucleotides with complementary single-stranded (ss) oligonucleotides, which are immobilised on the oxide surface of the transistor gate. This method allows direct, time-resolved and in situ detection of specific nucleic acid binding events without any labelling. We focus on the detection mechanism of our sensors by using oppositely charged polyelectrolytes (PAH and PSS) subsequently attached to the transistor structures.

CMOS DNA Sensor Array With Integrated A/D Conversion Based on Label-Free Capacitance Measurement

IEEE Journal of Solid-State Circuits, 2000

This paper presents a fully electronic label-free DNA chip in 0.5-m CMOS technology, with 5-V supply voltage, suitable for low-cost highly integrated applications. The chip features an array of 128 sensor sites with gold electrodes and integrated measurement, conditioning, multiplexing and analog-to-digital conversion circuitry. The circuits measure capacitance variations due to DNA hybridization on the gold electrodes which are bio-modified by covalently attaching probes of known sequence. Specificity, repeatability and parallel detection capability of the fabricated chip are successfully demonstrated.

Electronic Detection of Nucleic Acid Molecules with a Field-Effect Transistor

MRS Proceedings, 2004

ABSTRACTCurrently, systems for the detection of nucleic acid sequences, known as DNA-chips, are getting lots of attention. Such systems usually involve either an enzymatic or chemical labelling reaction as part of the detection process. The next generation of DNA-chips aims at a labelfree, fully electronic readout system. Several new approaches to signal generation that avoid a labelling step have been developed in recent years. Besides other surface sensitive measurements the possibility of electrochemical impedance and field-effect measurements for the detection of biomolecules have been discussed. The fully electronic detection of charged biomolecules based on the field-effect principle offers a labelfree method, which combines the unique sensitivity and selectivity of biomolecular recognition reactions with an electronic chip-based readout. In this approach one type of molecules is fixed at a surface and the biomolecular reaction with complementary molecules is detected by chang...

Active Field Effect Capacitive Sensors for High-throughput, Label-free Nucleic Acid Analysis

MRS Proceedings, 2008

We report a highly selective technique for rapid and label-free analysis of nucleic acid sample using Metal Oxide Semiconductor (MOS) capacitive sensors. The binding of charged macromolecules such as DNA on the surface of these Field Effect Devices modifies the charge distribution in the Semiconductor (Si) region of the sensor. These changes are manifested as a significant shift in the Capacitance-Voltage (C-V) characteristics measured across the device. The speed and selectivity of the detection process is enhanced by the use of external electric field of controlled intensity. This simple and high-throughput sensing technique holds promises for future electronic DNA arrays and Lab-on-a Chip devices.

A Low-Voltage and Label-Free Impedance-Based Miniaturized CMOS Biosensor for DNA Detection

Jurnal Teknologi, 2014

This study designs a low-voltage, label-free and fully integrated impedance-based biosensor using standard complementary metal oxide semiconductor (CMOS) technology to compute both capacitance and resistance of the electrode-electrolyte interface. The proposed biosensor circuit is composed of a common-gate transimpedance amplifier (CG-TIA) with two quadrature phase Gilbert cell double-balanced mixers and finally integrated with microelectrode using 0.18 µm Silterra CMOS technology process. The output value of the readout circuit was used to estimate the magnitude and phase of the measured admittance. The developed CG-TIA can achieve a gain of 88.6 dB up to a frequency of 50 MHz. The overall dynamic range was approximately 116 dB.

Electronic detection of DNA by its intrinsic molecular charge

Proceedings of the National Academy of Sciences, 2002

We report the selective and real-time detection of label-free DNA using an electronic readout. Microfabricated silicon field-effect sensors were used to directly monitor the increase in surface charge when DNA hybridizes on the sensor surface. The electrostatic immobilization of probe DNA on a positively charged poly-L-lysine layer allows hybridization at low ionic strength where field-effect sensing is most sensitive. Nanomolar DNA concentrations can be detected within minutes, and a single base mismatch within 12-mer oligonucleotides can be distinguished by using a differential detection technique with two sensors in parallel. The sensors were fabricated by standard silicon microtechnology and show promise for future electronic DNA arrays and rapid characterization of nucleic acid samples. This approach demonstrates the most direct and simple translation of genetic information to microelectronics.

Label-free DNA detection with a nanogap embedded complementary metal oxide semiconductor

Nanotechnology, 2011

A nanogap embedded complementary metal oxide semiconductor (NeCMOS) is demonstrated as a proof-of-concept for label-free detection of DNA sequence. When a partially carved nanogap between a gate and a silicon channel is filled with charged biomolecules, the gate dielectric constant and charges are changed. When the gate oxide thickness reduces, the threshold voltage is significantly affected by a change of the charges, whereas it is scarcely influenced by a change of the dielectric constant. In the case of DNA, those two factors act on the threshold voltage oppositely in an n-channel NeCMOS but collaboratively in a p-channel NeCMOS because of the negative charges of DNA. Hence, a p-channel NeCMOS with a thin gate oxide is more attractive for DNA detection because it enhances the shift of threshold voltage; that is, it improves the sensitivity of DNA detection. In addition, the shift of threshold voltage according to the nanogap length is also investigated and the longer nanogap shows more shift of the threshold voltage.