Sensitive Detection of Sweat Cortisol Using an Organic Electrochemical Transistor Featuring Nanostructured Poly(3,4-Ethylenedioxythiophene) Derivatives in the Channel Layer.

In this study, we examined the influence of functionalized poly(3,4-ethylenedioxythiophene) (PEDOT) nanostructures decorated on the channel layer of an organic electrochemical transistor (OECT) for the detection of sweat cortisol, an adrenocorticosteroid stress hormone. The OECT device featured a bilayer channel confined by a PEDOT:polystyrenesulfonate (PSS) underlayer and a nanostructure-decorated upper layer engineered from the monomers EDOT-COOH and EDOT-EG3 through template-free electrochemical polymerization. This molecular design allowed antibody conjugation using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide/N-hydroxysulfosuccinimide coupling through the carboxylic acid side chain, with EDOT-EG3 known to minimize nonspecific binding of biomolecules. We also engineered an OECT device having a channel area without any nanostructures to gain insight into the effect of the nanostructures on cortisol sensing. Our new nanostructure-embedded OECT device facilitated real-time detection of cortisol at concentrations ranging from 1 fg/mL to 1 µg/mL with a detection limit of 0.0088 fg/mL with good linearity (R2 = 0.9566), in addition to excellent selectivity toward cortisol among other structurally similar interfering compounds and high stability and reproducibility. With its rapid response for the detection of 100 ng/mL cortisol-spiked artificial sweat, this nanostructure-decorated OECT device has potential clinical practicality and utility in wearable sensors for future healthcare applications.

Molecular and nano structures of chiral PEDOT derivatives influence the enantiorecognition of biomolecules. In silico analysis of chiral recognition.

In this study we investigated the synergistic effects of the chirality (molecular structure) and surface morphology (nanostructure) of a newly designed sensing platform for the stereoselective recognition of biomolecules. We synthesized 3,4-ethylenedioxythiophene monomers presenting an OH functional group on the side chain (EDOT-OH) with either R or S chirality and then electropolymerized them in a template-free manner to engineer poly(EDOT-OH) nanotubes and smooth films with R or S chirality. We used a quartz crystal microbalance (QCM) to examine the differential binding of fetal bovine serum, RGD peptide, insulin, and (R)- and (S)-mandelic acid (MA) on these chiral polymeric platforms. All of these biomolecules bound stereoselectively and with greater affinity toward the nanotubes than to the smooth films. The sensitive chiral recognition of (S)- and (R)-MA on the (R)-poly(EDOT-OH) nanotube surface occurred with the highest chiral discrepancy ratio of 1.80. In vitro experiments revealed a greater degree of protein deposition from MCF-7 cells on the chiral nanotube surfaces. We employed ab initio molecular dynamics simulations and density functional theory calculations to investigate the mechanism underlying the sensitive chiral recognition between the chiral sensing platforms and the chiral analyte molecules.

Mechanotactic Activation of TGF-ß by PEDOT Artificial Microenvironments Triggers Epithelial to Mesenchymal Transition.

Epithelial to mesenchymal transition (EMT) is integral for cells to acquire metastatic properties, and ample evidence links it to bioorganic framework of the tumor microenvironment (TME). Hydroxymethyl-functionalized 3,4-ethylenedioxythiophene polymer (PEDOT-OH) enables construction of diverse nanotopography size and morphologies and is therefore exploited to engineer organic artificial microenvironments bearing nanodots from 300 to 1000 nm in diameter to understand spatiotemporal EMT regulation by biophysical components of the TME. MCF-7 breast cancer cells are cultured on these artificial microenvironments, and temporal regulation of cellular morphology and EMT markers is investigated. The results show that upon physical stimulation, cells on 300 nm artificial microenvironments advance to EMT and display a decreased extracellular matrix (ECM) protein secretion. In contrast, cells on 500 nm artificial microenvironments are trapped in EMT-imbalance. Interestingly, cells on 1000 nm artificial microenvironments resemble those on control surfaces. Upon further investigation, it is found that EMT induction is triggered via transforming growth factor ß (TGF-ß) and ECM cleaving protein, matrix metalloproteinease-9. Immunostaining EMT proteins highlighted that EMT induction is achieved through attenuation of cell-cell and cell-microenvironment adhesions. The physical stimulation-induced TGF-ß perturbation can have a profound impact on the understanding of tumor-promoting signaling cascades originated by cellular microenvironment.