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 biomolecules in full ionic strength biological fluids, with high specificity and selectivity, over a dynamic range of concentrations with unprecedented 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, a common genetic disorder. Three phenylalanine-specific DNA sequences were investigated to determine sensor responses contingent on different primary base sequences, secondary structures, and target affinities. In parallel, to elucidate fundamental sensing mechanisms of aptamer-FETs, we worked with aptamers targeting a neutral target, glucose. Glucose aptamer sequence variants (i.e. sequences with different stem lengths) were used to investigate the relationship between distances from FET surfaces and conductance changes. Elucidating aptamer-FET sensing mechanisms is necessary for their ultimate use in biochemical signaling in vivo and for clinical point-of-care applications.

Aptamer field-effect transistors for small-molecule detection

256th National Meeting (2018)

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