Label-Free DNA Detection Using a Charge Sensitive CMOS Microarray Sensor Chip

Abstract

This paper presents label-free DNA detection using a charge sensitive microarray sensor. The microarray sensor, fabricated with a standard CMOS process, contains 1024 detector elements integrated together with their readout circuit in a single chip. This microarray sensor chip is developed for biosensing applications involving label-free detection of charged particles and molecules with improved sensitivity. The proposed chip is used for the detection of DNA immobilization and hybridization by directly sensing the phosphate backbone charge of DNA molecules. The sensing part of the chip consists of an array of 7 µm × 7 µm capacitive metal electrodes arranged in 32 × 32 format with a pitch of 15 µm, which allows implementation of a portable and low-cost microarray sensor. The sensitivity of the microarray sensor is improved compared with other direct charge sensing CMOS biosensors, using low-noise detection and amplification circuits, and implementing correlated double sampling, which reduces the input referred rms noise level down to 6.8 electrons (e − ). Due to this low noise level, detection of DNA having 1 pM concentration is achieved, showing that the chip is much more sensitive than its counterparts, and even as sensitive as conventional fluorescence or gravimetric detection techniques. A dynamic range of 70 dB is achieved, along with the low noise level. The tests were performed with 10 base pairs DNA in 13-µM probe (5'-TCTCACCTTC-3') and 1-pM target (3'-AGAGTGGAAG-5') oligomer solutions. In both cases, charges of the DNA molecules interacting with the surface were successfully detected.

Silicon-Based Sensors for Biomedical Applications: A Review

“…The detection of urea, DNA and other proteins was done using these sensors via conductimetric measurements. Musayav et al [64] developed a microarray sensor for detecting the direct phosphate backbone charge of DNA molecules. Capacitive metallic electrodes with dimensions of 7 μm × 7 μm had been utilised to develop the array by arranging the electrode with a pitch of 15 μm.…”

Computer Simulation of a Surface Charge Nanobiosensor with Internal Signal Integration

“…Nanobiosensors are analytical devices that combine a biologically sensitive element with a nanostructured transducer, and are widely used for molecular detection. They show certain advantages [7][8][9][10][11][12][13] due to their inherent specificity, simplicity, and quick responses. By design, nanobiosensors are hybrid devices in which an organic object is embedded in a nano or microelectronic semiconductor device.…”

Label‐Free DNA Sensors Based on Field‐Effect Transistors with Semiconductor of Carbon Materials

“…The small dimension of the Si-FET sensors endows the ability to microfabricate them in large numbers in a single chip. [18] However, the development of Si-FET sensor still has bottlenecks, such as material-type limitation, incompatibility to biospecies, high cost of Si processing technology, etc. Therefore, seeking alternative semiconductor material and device technologies for high performance and low cost FET DNA sensor is still necessary.…”