We have designed and developed ultrathin-film field-effect transistors (FETs) coupled to rationally designed and chemically synthesized oligonucleotide sequences with molecular recognition capabilities, termed aptamers, for the detection of a diverse range of biologically important small-molecule targets (e.g., neurotransmitters, amino acids, sugars, lipids). Upon target capture, aptamers undergo conformational changes that redistribute charge densities on FET surfaces resulting in measurable changes in conductance. We demonstrate the detection of targets in full ionic strength biological fluids, with high specificity and selectivity, over large concentration ranges with low detection limits. Using this platform, we are developing sensors for the direct detection of the amino acid phenylalanine for potential point-of-care use for patients with phenylketonuria (PKU), a common genetic disorder that results in elevated and potentially harmful levels of phenylalanine in the blood and brain. Three phenylalanine-specific DNA sequences were investigated to determine sensor responses contingent on different primary base sequences, secondary structures, and target affinities. Phenylalanine aptamer-FETs showed high sensitivity and selectivity towards phenylalanine versus similarly structured molecules, and were able to differentiate physiological phenylalanine concentrations in serum from mice treated with a phenylalanine hydroxylase inhibitor (i.e., a PKU mouse model). In parallel, we have extended this FET biosensor platform for the detection and discrimination of single-nucleotide polymorphisms. We demonstrate the ability of DNA-functionalized FETs to distinguish hybridization between fully complementary DNA sequences, and analogous sequences with different types and locations of SNPs. Performing FET measurements under physiologically relevant conditions and elucidating sensing mechanisms is necessary for ultimate use in disease diagnostics and clinical point-of-care applications.

Nucleic-acid-functionalized field-effect transistors for biomedical applications

2019 Fall National Meeting

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