Divalent Cation Dependence Enhances Dopamine Aptamer Biosensing

Abstract

Oligonucleotide receptors (aptamers), which change conformation upon target recognition, enable electronic biosensing under high ionic-strength conditions when coupled to field-effect transistors (FETs). Because highly negatively charged aptamer backbones are influenced by ion content and concentration, biosensor performance and target sensitivities were evaluated under application conditions. For a recently identified dopamine aptamer, physiological concentrations of Mg 2+ and Ca 2+ in artificial cerebrospinal fluid produced marked potentiation of dopamine FET-sensor responses. By comparison, divalent cationassociated signal amplification was not observed for FET sensors functionalized with a recently identified serotonin aptamer or a previously reported dopamine aptamer. Circular dichroism spectroscopy revealed Mg 2+ -and Ca 2+ -induced changes in target-associated secondary structure for the new dopamine aptamer, but not the serotonin aptamer nor the old dopamine aptamer. Thioflavin T displacement corroborated the Mg 2+ dependence of the new dopamine aptamer for target detection. These findings imply allosteric binding interactions between divalent cations and dopamine for the new dopamine aptamer. Developing and testing sensors in ionic environments that reflect intended applications are best practices for identifying aptamer candidates with favorable attributes and elucidating sensing mechanisms.

Ultrasensitive Dopamine Detection with Graphene Aptasensor Multitransistor Arrays

“…2C). These results lend further support to previous observations reporting potential alterations of the secondary structure of this aptamer in the presence of Ca 2+ and Mg 2+ , which are present in both CSF and aCSF [38], [41]. The excess of positive charges near the graphene channel upon dopamine binding may also explain the significant increase of the dynamic detection range in aCSF, because each detection event may add multiple positive charges within the Debye length.…”

“…2B). The observed positive shifts in V DIRAC with increasing concentrations of dopamine are hypothesized to occur due to reorientation of the negative charges of the DNA aptamer phosphate backbone near the EG-gFETs’ channels upon dopamine binding [41] (Fig. 2B).…”

Pre-equilibrium biosensors: A new approach towards rapid and continuous molecular measurements

“…Figure 6b. Even for the demanding sensing requirements chosen for this example, we find that the kinetic parameters are within the expected range of typical antibodies 30,31 and that the noise requirement is tractable, based on the sensing performance of published biosensors [32][33][34][35][36][37][38][39] .This supports the idea that antibodies should be viable receptors for use in a real-time insulin sensor.…”

Wearable aptamer-field-effect transistor sensing system for noninvasive cortisol monitoring

“…S5, B and E). We investigated target-induced changes in aptamer secondary structural motifs using circular dichroism spectroscopy, as in our previous work ( 27 , 28 , 43 ). Upon target association, the cortisol aptamer showed a spectral shift and decrease in intensity in the major positive band (fig.…”