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Cmos integrated sensor readout circuitry for dna detection applications

Musayev, Javid
his study presents a CMOS integrated sensor chip suitable for sensing biological samples like DNA. The sensing part of the chip consists of a 32 X 32 pixel array with a 15 µm pixel pitch. Pixels have 5 µm X 5 µm detector electrodes implemented with the top metal of the CMOS process, and they are capable of detecting charge transferred or induced on those electrodes with a very high sensitivity. This study also includes development of an external electronics containing ADC for analog to digital data conversion. This external circuitry is implemented on a PCB compatible with the Opal Kelly XM3010 FPGA that provides data storage and transfer to PC. The measured noise of the overall system is 6.7 e- (electrons), which can be shrunk down to even 5.1 e- with an over sampling rate. This kind of sensitivity performance is very suitable for DNA detection, as a single nucleotide of a DNA contains 1 or 2 e- and as 10 to 20 base pair long DNA’s are usually used in microarray applications. The measured dynamic range of the system is 71 dB, in other words, at most 24603 e- per frame (20 ms) can be detected. The measured leakage is 31 e-/frame, but this does not have a dramatic effect on the sensitivity of the system, noting that the leakage is a predictable quantity. DNA detection tests are performed with the chip in addition to electronic performance measurements. The surface of the chip is covered with a nitride passivation layer to prevent the pixel crosstalk and is modified with an APTES polymer for suitable DNA immobilization. DNA immobilization and hybridization tests are performed with 5’-TCTCACCTTC-3’ probe and its complementary 3’-AGAGTGGAAG-5’ target sequences. Hybridization performed in 1 pM solution is shown to have a larger steady state leakage than the immobilization in a 13 µM solution, implying the ability to differentiate between the full match and full mismatch sequences. To best of our knowledge, the measured pM sensitivity has not yet been reported with any label free CMOS DNA microarrays in literature, and it is comparable with the sensitivity of techniques like QCM or the fluorescence imaging. The 1 pM sensitivity is not a theoretical limit of the sensor, since theoretically the sensitivity level of 6.7 e- can offer much better results, down to the aM level, as far as the noise of electronics is considered, nevertheless the sensitivity is expected to be limited by DNA immobilization and hybridization probabilities which are determined by the surface modification technique and applied protocol. Improving those can lead to much smaller detection limits, such as aM level as stated above.