Nano-bioelectronics represents a rapidly expanding interdisciplinary field that combines nanomaterials with biology and electronics, and in so doing, offers the potentials to overcome existing challenges in bioelectronics. In particular, shrinking electronic transducer dimensions to the nanoscale and making their properties appear more biological can yield significant improvements in the sensitivity and biocompatibility, and thereby open up opportunities in fundamental biology and healthcare. This review emphasizes recent advances in nano-bioelectronics enabled with semiconductor nanostructures, including silicon nanowires (SiNWs), carbon nanotubes (CNTs), and graphene. First, the synthesis and electrical properties of these nanomaterials are discussed in the context of bioelectronics. Second, affinity-based nano-bioelectronic sensors for highly sensitive analysis of biomolecules are reviewed. In these studies, semiconductor nanostructures as transistor-based biosensors are discussed from fundamental device behavior through sensing applications and future challenges. Third, the complex interface between nanoelectronics and living biological systems, from single cells to live animals are reviewed. This discussion focuses on representative advances in electrophysiology enabled using semiconductor nanostructures and their nanoelectronic devices for cellular measurements through emerging work where arrays of nanoelectronic devices are incorporated within three-dimensional cell networks that define synthetic and natural tissues. Last, some challenges and exciting future opportunities are discussed.
Nanomaterial-based field-effect transistor (FET) sensors are capable of label-free real-time chemical and biological detection with high sensitivity and spatial resolution, although direct measurements in high-ionic-strength physiological solutions remain challenging due to the Debye screening effect. Recently, we demonstrated a general strategy to overcome this challenge by incorporating a biomoleculepermeable polymer layer on the surface of silicon nanowire FET sensors. The permeable polymer layer can increase the effective screening length immediately adjacent to the device surface and thereby enable real-time detection of biomolecules in high-ionic-strength solutions. Here, we describe studies demonstrating both the generality of this concept and application to specific protein detection using graphene FET sensors. Concentration-dependent measurements made with polyethylene glycol (PEG)-modified graphene devices exhibited real-time reversible detection of prostate specific antigen (PSA) from 1 to 1,000 nM in 100 mM phosphate buffer. In addition, comodification of graphene devices with PEG and DNA aptamers yielded specific irreversible binding and detection of PSA in pH 7.4 1x PBS solutions, whereas control experiments with proteins that do not bind to the aptamer showed smaller reversible signals. In addition, the active aptamer receptor of the modified graphene devices could be regenerated to yield multiuse selective PSA sensing under physiological conditions. The current work presents an important concept toward the application of nanomaterial-based FET sensors for biochemical sensing in physiological environments and thus could lead to powerful tools for basic research and healthcare.field-effect transistor | Debye screening | surface modification | DNA aptamer receptor | polyethylene glycol N anoelectronic biosensors offer broad capabilities for label-free high-sensitivity real-time detection of biological species that are important to both fundamental research and biomedical applications (1-6). In particular, field-effect transistor (FET) biosensors configured from semiconducting nanowires (1, 2), single-walled carbon nanotubes (1, 3, 4), and graphene (1, 5, 6) have been extensively investigated since the first report of real-time protein detection using silicon nanowire devices (7). Subsequent studies have demonstrated highly sensitive and in some cases multiplexed detection of key analytes, including protein disease markers (8-10), nucleic acids (11-13), and viruses (14), as well as detection of protein-protein interactions (8,(15)(16)(17) and enzymatic activity (8).The success achieved with nanomaterial-based FET biosensors has been limited primarily to measurements in relatively low-ionicstrength nonphysiological solutions due to the Debye screening length (18,19). In short, the screening length in physiological solutions, <1 nm, reduces the field produced by charged macromolecules at the FET surface and thus makes real-time label-free detection difficult. The first method reported to overcome this ...
Semiconductor nanowire (NW) devices that can address intracellular electrophysiological events with high sensitivity and spatial resolution are emerging as key tools in nanobioelectronics. Intracellular delivery of NWs without compromising cellular integrity and metabolic activity has, however, proven difficult without external mechanical forces or electrical pulses. Here, we introduce a biomimetic approach in which a cell penetrating peptide, the trans-activating transcriptional activator (TAT) from human immunodeficiency virus 1, is linked to the surface of Si NWs to facilitate spontaneous internalization of NWs into primary neuronal cells. Confocal microscopy imaging studies at fixed time points demonstrate that TAT-conjugated NWs (TAT-NWs) are fully internalized into mouse hippocampal neurons, and quantitative image analyses reveal an ca. 15% internalization efficiency. In addition, live cell dynamic imaging of NW internalization shows that NW penetration begins within 10-20 min after binding to the membrane and that NWs become fully internalized within 30-40 min. The generality of cell penetrating peptide modification method is further demonstrated by internalization of TAT-NWs into primary dorsal root ganglion (DRG) neurons.
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