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

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.