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Bioelectronic devices and components made from soft, polymer-based and hybrid electronic materials form natural interfaces with the human body. Advances in the molecular design of stretchable dielectric, conducting and semiconducting polymers, as well as their composites with various metallic and inorganic nanoscale or microscale materials, have led to more unobtrusive and conformal interfaces with tissues and organs. Nonetheless, technical challenges associated with functional performance, stability and reliability of integrated soft bioelectronic systems still remain. This Review discusses recent progress in biomedical applications of soft organic and hybrid electronic materials, device components and integrated systems for addressing these challenges. We first discuss strategies for achieving soft and stretchable devices, highlighting molecular and materials design concepts for incorporating intrinsically stretchable functional materials. We next describe design strategies and considerations on wearable devices for on-skin sensing and prostheses. Moving beneath the skin, we discuss advances in implantable devices enabled by materials and integrated devices with tissue-like mechanical properties. Finally, we summarize strategies used to build standalone integrated systems and whole-body networks to integrate wearable and implantable bioelectronic devices with other essential components, including wireless communication units, power sources, interconnects and encapsulation. 

Wearable technologies for personalized monitoring require sensors that track biomarkers often present at low levels. Cortisol—a key stress biomarker—is present in sweat at low nanomolar concentrations. Previous wearable sensing systems are limited to analytes in the micromolar-millimolar ranges. To overcome this and other limitations, we developed a flexible field-effect transistor (FET) biosensor array that exploits a previously unreported cortisol aptamer coupled to nanometer-thin-film In 2 O 3 FETs. Cortisol levels were determined via molecular recognition by aptamers where binding was transduced to electrical signals on FETs. The physiological relevance of cortisol as a stress biomarker was demonstrated by tracking salivary cortisol levels in participants in a Trier Social Stress Test and establishing correlations between cortisol in diurnal saliva and sweat samples. These correlations motivated the development and on-body validation of an aptamer-FET array–based smartwatch equipped with a custom, multichannel, self-referencing, and autonomous source measurement unit enabling seamless, real-time cortisol sweat sensing. 

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.