Synthetic Nanoelectronic Probes for Biological Cells and Tissues

Research at the interface between nanoscience and biology could yield breakthroughs in fundamental science and lead to revolutionary technologies. In this review, we focus on the interfaces between nanoelectronics and biology. First, we discuss nanoscale field effect transistors (nanoFETs) as probes to study cellular systems; specifically, we describe the development of nanoFETs that are comparable in size to biological nanostructures involved in communication through synthesized nanowires. Second, we review current progress in multiplexed extracellular sensing using planar nanoFET arrays. Third, we describe the designs and implementation of three distinct nanoFETs used to perform the first intracellular electrical recording from single cells. Fourth, we present recent progress in merging electronic and biological systems at the three-dimensional tissue level by use of macro-porous nanoelectronic scaffolds. Finally, we discuss future developments in this research area, unique challenges and opportunities, and the tremendous impact these nanoFET-based technologies might have on biological and medical sciences.Chemistry and Chemical BiologyEngineering and Applied Science

Bridging the Gap—Thermofluidic Designs for Precision Bioelectronics

Bioelectronics, the merging of biology and electronics, can monitor and modulate biological behaviors across length and time scales with unprecedented capability. Current bioelectronics research largely focuses on devices’ mechanical properties and electronic designs. However, the thermofluidic control is often overlooked, which is noteworthy given the discipline's importance in almost all bioelectronics processes. It is believed that integrating thermofluidic designs into bioelectronics is essential to align device precision with the complexity of biofluids and biological structures. This perspective serves as a mini roadmap for researchers in both fields to introduce key principles, applications, and challenges in both bioelectronics and thermofluids domains. Important interdisciplinary opportunities for the development of future healthcare devices and precise bioelectronics will also be discussed

Probing the electronic properties of the electrified silicon/water interface by combining simulations and experiments

Silicon (Si) is broadly used in electrochemical and photoelectrochemical devices, where the capacitive and Faradaic reactions at the Si/water interfaces are critical for signal transduction or noise generation. However, probing the electrified Si/water interface at the microscopic level remains a challenging task. Here we focus on hydrogenated Si surfaces in contact with water, relevant to transient electronics and photoelectrochemical modulation of biological cells and tissues. We show that by carrying out first-principles molecular dynamics simulations of the Si(100)/water interface in the presence of an electric field we can realistically correlate the computed flat-band potential and tunneling current images at the interface with experimentally measured capacitive and Faradaic currents. Specifically, we validate our simulations in the presence of bias by performing pulsed chronoamperometry measurements on Si wafers in solution. Consistent with prior experiments, our measurements and simulations indicate the presence of voltage-dependent capacitive currents at the interface. We also find that Faradaic currents are weakly dependent on the applied bias, which we relate to surface defects present in newly prepared samples

Outside Looking In: Nanotube Transistor Intracellular Sensors

Nanowire-based field-effect transistors, including devices with planar and three-dimensional configurations, are being actively explored as detectors for extra- and intracellular recording due to their small size and high sensitivities. Here we report the synthesis, fabrication, and characterization of a new needle-shaped nanoprobe based on an active silicon nanotube transistor, ANTT, that enables high-resolution intracellular recording. In the ANTT probe, the source/drain contacts to the silicon nanotube are fabricated on one end, passivated from external solution, and then time-dependent changes in potential can be recorded from the opposite nanotube end via the solution filling the tube. Measurements of conductance versus water-gate potential in aqueous solution show that the ANTT probe is selectively gated by potential changes within the nanotube, thus demonstrating the basic operating principle of the ANTT device. Studies interfacing the ANTT probe with spontaneously beating cardiomyocytes yielded stable intracellular action potentials similar to those reported by other electrophysiological techniques. In addition, the straightforward fabrication of ANTT devices was exploited to prepare multiple ANTT structures at the end of single probes, which enabled multiplexed recording of intracellular action potentials from single cells and multiplexed arrays of single ANTT device probes. These studies open up unique opportunities for multisite recordings from individual cells through cellular networks.Chemistry and Chemical Biolog

Intracellular Recordings of Action Potentials by an Extracellular Nanoscale Field-Effect Transistor

The ability to make electrical measurements inside cells has led to many important advances in electrophysiology. The patch clamp technique, in which a glass micropipette filled with electrolyte is inserted into a cell, offers both high signal-to-noise ratio and temporal resolution. Ideally, the micropipette should be as small as possible to increase the spatial resolution and reduce the invasiveness of the measurement, but the overall performance of the technique depends on the impedance of the interface between the micropipette and the cell interior, which limits how small the micropipette can be. Techniques that involve inserting metal or carbon microelectrodes into cells are subject to similar constraints. Field-effect transistors (FETs) can also record electric potentials inside cells, and because their performance does not depend on impedance, they can be made much smaller than micropipettes and microelectrodes. Moreover, FET arrays are better suited for multiplexed measurements. Previously, we have demonstrated FET-based intracellular recording with kinked nanowire structures, but the kink configuration and device design places limits on the probe size and the potential for multiplexing. Here, we report a new approach in which a $SiO_2$ nanotube is synthetically integrated on top of a nanoscale FET. This nanotube penetrates the cell membrane, bringing the cell cytosol into contact with the FET, which is then able to record the intracellular transmembrane potential. Simulations show that the bandwidth of this branched intracellular nanotube FET (BIT-FET) is high enough for it to record fast action potentials even when the nanotube diameter is decreased to 3 nm, a length scale well below that accessible with other methods. Studies of cardiomyocyte cells demonstrate that when phospholipid-modified BIT-FETs are brought close to cells, the nanotubes can spontaneously penetrate the cell membrane to allow the full-amplitude intracellular action potential to be recorded, thus showing that a stable and tight seal forms between the nanotube and cell membrane. We also show that multiple BIT-FETs can record multiplexed intracellular signals from both single cells and networks of cells.Chemistry and Chemical BiologyEngineering and Applied SciencesPhysic

Macroporous nanowire nanoelectronic scaffolds for synthetic tissues

available in PMC 2013 April 11.The development of three-dimensional (3D) synthetic biomaterials as structural and bioactive scaffolds is central to fields ranging from cellular biophysics to regenerative medicine. As of yet, these scaffolds cannot electrically probe the physicochemical and biological microenvironments throughout their 3D and macroporous interior, although this capability could have a marked impact in both electronics and biomaterials. Here, we address this challenge using macroporous, flexible and free-standing nanowire nanoelectronic scaffolds (nanoES), and their hybrids with synthetic or natural biomaterials. 3D macroporous nanoES mimic the structure of natural tissue scaffolds, and they were formed by self-organization of coplanar reticular networks with built-in strain and by manipulation of 2D mesh matrices. NanoES exhibited robust electronic properties and have been used alone or combined with other biomaterials as biocompatible extracellular scaffolds for 3D culture of neurons, cardiomyocytes and smooth muscle cells. Furthermore, we show the integrated sensory capability of the nanoES by real-time monitoring of the local electrical activity within 3D nanoES/cardiomyocyte constructs, the response of 3D-nanoES-based neural and cardiac tissue models to drugs, and distinct pH changes inside and outside tubular vascular smooth muscle constructs.National Institutes of Health (U.S.) (Director’s Pioneer award)McKnight Foundation (Technological Innovations in Neurosciences Award)Boston Children's Hospital (Biotechnology Research Endowment)National Institutes of Health (U.S.) (DE013023)National Institutes of Health (U.S.) (DE016516

Optimizing nitrogen application position to change root distribution in soil and regulate maize growth and yield formation in a wide–narrow row cropping system: pot and field experiments

The wide-and narrow-row cropping technology used for maize has the advantages of protecting cultivated soil and improving the population structure in maize fields. However, the relationship between nitrogen application position and root interactions has not been determined. Through pot and field experiments, we evaluated the effects of two nitrogen application positions ((narrow row nitrogen application (RC) and wide row nitrogen application (RN)) and two nitrogen application regimens ((high nitrogen(HN) and low nitrogen(LN)) on root growth and yield composition of wide-narrow row maize during the flowering and harvest stages. In field experiments, RC increased the biomass, length and surface area of competing roots (narrow-row roots, CR) at the flowering stage. The yield and agronomic efficiency of N(AEN) and partial factor productivity of N(PFPN) were increased by RN compared to RC under HN, However, the AEN under LN was significantly lower; There was no significant effect on maize growth and biomass allocation at the same level of application of N. At the flowering stage, the results of CR and non-competing roots (wide-row roots, NCR) was consistent under pot experiments and the field experiments, and the yield under RN was also higher than that under RC, although the difference was not significant. Furthermore, according to the principal component analysis and correlation analysis, the competing roots were the main factor influencing yield and AEN. In conclusion, our study showed that RN is a useful fertilization method to improve overall productivity. All in all, how roots coordinate neighbors and nitrogen spatial heterogeneity is a complex ecological process, and its trophic behavior deserves further study

Distributed interfacing by nanoscale photodiodes enables single-neuron light activation and sensory enhancement in 3D spinal explants

Among emerging technologies developed to interface neuronal signaling, engineering electrodes at the nanoscale would yield more precise biodevices opening to progress in neural circuit investigations and to new therapeutic potential. Despite remarkable progress in miniature electronics for less invasive neurostimulation, most nano-enabled, optically triggered interfaces are demonstrated in cultured cells, which precludes the studies of natural neural circuits. We exploit here free-standing silicon-based nanoscale photodiodes to optically modulate single, identified neurons in mammalian spinal cord explants. With near-infrared light stimulation, we show that activating single excitatory or inhibitory neurons differently affects sensory circuits processing in the dorsal horn. We successfully functionalize nano-photodiodes to target single molecules, such as glutamate AMPA receptor subunits, thus enabling light activation of specific synaptic pathways. We conclude that nano-enabled neural interfaces can modulate selected sensory networks with low invasiveness. The use of nanoscale photodiodes can thus provide original perspective in linking neural activity to specific behavioral outcome

Roadmap on semiconductor-cell biointerfaces.

This roadmap outlines the role semiconductor-based materials play in understanding the complex biophysical dynamics at multiple length scales, as well as the design and implementation of next-generation electronic, optoelectronic, and mechanical devices for biointerfaces. The roadmap emphasizes the advantages of semiconductor building blocks in interfacing, monitoring, and manipulating the activity of biological components, and discusses the possibility of using active semiconductor-cell interfaces for discovering new signaling processes in the biological world

Periplasmic biomineralization for semi-artificial photosynthesis

Semiconductor-based biointerfaces are typically established either on the surface of the plasma membrane or within the cytoplasm. In Gram-negative bacteria, the periplasmic space, characterized by its confinement and the presence of numerous enzymes and peptidoglycans, offers additional opportunities for biomineralization, allowing for nongenetic modulation interfaces. We demonstrate semiconductor nanocluster precipitation containing single- and multiple-metal elements within the periplasm, as observed through various electron- and x-ray-based imaging techniques. The periplasmic semiconductors are metastable and display defect-dominant fluorescent properties. Unexpectedly, the defect-rich (i.e., the low-grade) semiconductor nanoclusters produced in situ can still increase adenosine triphosphate levels and malate production when coupled with photosensitization. We expand the sustainability levels of the biohybrid system to include reducing heavy metals at the primary level, building living bioreactors at the secondary level, and creating semi-artificial photosynthesis at the tertiary level. The biomineralization-enabled periplasmic biohybrids have the potential to serve as defect-tolerant platforms for diverse sustainable applications