Nanowire-Enabled Bioelectronics

Abstract

Bioelectronics explores the use of electronic devices for applications in signal transduction at their interfaces with biological systems. The miniaturization of the bioelectronic systems has enabled seamless integration at these interfaces and is providing new scientific and technological opportunities. In particular, nanowire-based devices can yield smaller sized and unique geometry detectors that are difficult to access with standard techniques, and thereby can provide advantages in sensitivity with reduced invasiveness. In this review, we focus on nanowire-enabled bioelectronics. First, we provide an overview of synthetic studies for designed growth of semiconductor nanowires of which structure and composition are controlled to enable key elements for bioelectronic devices. Second, we review nanowire field-effect transistor sensors for highly sensitive detection of biomolecules, their applications in diagnosis and drug discovery, and methods for sensitivity enhancement. We then turn to recent progress in nanowire-enabled studies of electrogenic cells, including cardiomyocytes and neurons. Representative advances in electrical recording using nanowire electronic devices for single cell measurements, cell network mapping, and three-dimensional recordings of synthetic and natural tissues, and in vivo brain mapping are highlighted. Finally, we overview the key challenges and opportunities of nanowires for fundamental research and translational applications.

Keywords: Bioelectronics; Biosensor; Brain mapping; Electrophysiology; Nanowire.

Fig. 1.

Structure-controlled synthesis of nanowires. Top, schematic illustration of VLS growth of NWs. Vapor phase reactants undergo nucleation and growth of crystals in the presence of metal nanoparticle catalyst. a, Axial heterostructures. Switching dopants and/or modulating reactor pressure during NW growth enables control of NW structure in the axial direction. b, Branched/tree-like structures. Sequential deposition of metal catalysts on synthesized NWs enables branched and tree-like heterostructures. c, Radial heterostructures. Uniform layer-by-layer deposition on NWs enables control of NW structure in the radial direction.

Fig. 2.

Nanowire biosensors. a, A NW FET biosensor for specific detection. Binding of charged analytes yields a change in the NW conductance. b, Conductance changes during association and dissociation phases of biomolecules on NWs. c, Parallel detection. Left, parallel detection by NW devices modified with different protein receptors. Right, conductance vs. time data for simultaneous detection of different proteins. d, Cancer detection. Left, telomerase detection and incorporation of activated nucleotides, dNTPs. Middle, conductance vs. time data for telomerase detection (point 1), and subsequent addition of dNTPs (point 2). Right, conductance vs. time data for telomerase detection (point 1) and inhibition of telomerase elongation (point 2). e, Signal amplification. Top, biomarker detection with the help of exponential DNA amplification with polymerase chain reaction (PCR) process. The protein sensing is translated to pH measurement by NW FET sensors. Bottom, pH sensing response by NW FETs vs. IL-2 biomarker concentration with immuno-PCR on NWs. f, Detection in high ionic strength solutions. Top, PEG surface modification on NW devices. Bottom, conductance vs. time data from devices with and without PEG modification in high ionic strength solutions. Panel c and d are adapted with permission from REF. [61], Macmillan Publishers Limited. Panel e is adapted with permission from REF. [62], American Chemical Society. Panel f is adapted with permission from REF. [63], American Chemical Society.

Fig. 3.

Cell electrophysiology. a, Extracellular electrical recording and biosensing. Top, a neuronal axon aligned on an array of NW devices. Lower left, a tight seal formed between the NW and neuronal membrane. Lower middle, axial NW heterostructures with a sensing region on the same length scale with a single ion channel. Lower right, neurotransmitter detection at a neuronal synapse. b, Intracellular electrical recording and biosensing. Top, intracellular recording using a patch pipette and a kinked NW probe penetrating cell membrane. Bottom, biochemical sensing with FET NWs intracellularly penetrated through membrane for detecting and monitoring in situ kinetics of biomolecules in live cells.

Fig. 4.

Tissue electrophysiology. a, Engineered tissues. NW probe arrays interfaced with biological tissue could enable network-level parallel and scalable recording for extended time periods. b, In vivo implants. Ultra-flexible tissue-like electronics embedded with multiple NW devices can be injected into a rodent brain with a syringe needle. The highly porous structure allows seamless interpenetration with neural networks and enables chronic recording of brain activity.