Aptamer–field-effect transistors overcome Debye length limitations for small-molecule sensing

Abstract

Molecular binding to receptors on the surface of field-effect transistors (FETs) can be sensed through changes in transconductance. However, the saline solutions typically used with biomolecules create an electrical double layer that masks any events that occur within about 1 nanometer from the surface. Nakatsuka et al. overcame this limitation by using binding to large, negatively charged DNA stem loop structures that, upon ligand binding, cause conformational changes that can be sensed with an FET, even in solutions with high ionic strength. The authors demonstrate the sensing of charged molecules such as dopamine in artificial cerebrospinal fluid as well as neutral molecules such as glucose and zwitterion molecules like sphingosine-1-phosphate. Science , this issue p. 319 Large conformational changes induced in charged DNA stem-loop receptors can be sensed in high–ionic strength solutions.Detection of analytes by means of field-effect transistors bearing ligand-specific receptors is fundamentally limited by the shielding created by the electrical double layer (the “Debye length” limitation). We detected small molecules under physiological high–ionic strength conditions by modifying printed ultrathin metal-oxide field-effect transistor arrays with deoxyribonucleotide aptamers selected to bind their targets adaptively. Target-induced conformational changes of negatively charged aptamer phosphodiester backbones in close proximity to semiconductor channels gated conductance in physiological buffers, resulting in highly sensitive detection. Sensing of charged and electroneutral targets (serotonin, dopamine, glucose, and sphingosine-1-phosphate) was enabled by specifically isolated aptameric stem-loop receptors.