Arrays of field-effect transistors are fabricated from chemical vapor deposition grown graphene (GFETs) and label-free detection of DNA hybridization performed down to femtomolar concentrations. A process is developed for large-area graphene sheets, which includes a thin Al 2 O 3 layer, protecting the graphene from contamination during photolithographic patterning and a SiO x capping for biocompatibility. It enables fabrication of high-quality transistor arrays, exhibiting stable close-to-zero Dirac point voltages under ambient conditions. Passivation of the as-fabricated chip with a layer composed of two different oxides avoids direct electrochemical contact between the DNA solutions and the graphene layer during hybridization detection. DNA probe molecules are electrostatically immobilized via poly-l-lysine coating of the chip surface. Adsorption of this positively charged polymer induces a positive shift of the Dirac point and subsequent immobilization of negatively charged DNA probes induces a negative shift. Spatially resolved hybridization of DNA sequences is performed on the GFET arrays. End-point as well as real-time in situ measurements of hybridization are achieved. A detection limit of 10 fm is observed for hybridization of 20-nucleotide DNA targets. Typical voltage signals are around 100 mV and spurious drifts below 1 mV per hour.
We describe an approach to substituting a fluorescence microarray with a surface made of an arrangement of electrolyte-gated field effect transistors. This was achieved using a dedicated blocking of non-specific interactions and comparing threshold voltage shifts of transistors exhibiting probe molecules of different base sequence. We apply the approach to detection of the 35delG mutation, which is related to non-syndromic deafness and is one of the most frequent mutations in humans. The process involves barcode sequences that are generated by Tas-PCR, a newly developed replication reaction using polymerase blocking. The barcodes are recognized by hybridization to surface attached probes and are directly detected by the semiconductor device.
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