Interfacing nanoelectronic devices with cell membranes can enable multiplexed detection of fundamental biological processes (such as signal transduction, electrophysiology, and import/export control) even down to the single ion channel level, which can lead to a variety of applications in pharmacology and clinical diagnosis. Therefore, it is necessary to understand and control the chemical and electrical interface between the device and the lipid bilayer membrane. Here, we develop a simple bottom-up approach to assemble tethered bilayer lipid membranes (tBLMs) on silicon wafers and glass slides, using a covalent tether attachment chemistry based on silane functionalization, followed by step-by-step stacking of two other functional molecular building blocks (oligo-poly(ethylene glycol) (PEG) and lipid). A standard vesicle fusion process was used to complete the bilayer formation. The monolayer synthetic scheme includes three well-established chemical reactions: self-assembly, epoxy-amine reaction, and EDC/NHS cross-linking reaction. All three reactions are facile and simple and can be easily implemented in many research labs, on the basis of common, commercially available precursors using mild reaction conditions. The oligo-PEG acts as the hydrophilic spacer, a key role in the formation of a homogeneous bilayer membrane. To explore the broad applicability of this approach, we have further demonstrated the formation of tBLMs on three common classes of (nano)electronic biosensor devices: indium-tin oxide-coated glass, silicon nanoribbon devices, and high-density single-walled carbon nanotubes (SWNT) networks on glass. More importantly, we incorporated alemethicin into tBLMs and realized the real-time recording of single ion channel activity with high sensitivity and high temporal resolution using the tBLMs/SWNT network transistor hybrid platform. This approach can provide a covalently bonded lipid coating on the oxide layer of nanoelectronic devices, which will enable a variety of applications in the emerging field of nanoelectronic interfaces to electrophysiology.Keywords: biosensor; glass slide; indium-tin oxide; silicon nanoribbon; silicon wafer; single-walled carbon nanotube film; tethered bilayer lipid membranes;

•The surface charge of mitochondria induces a change in the conductance of carbon nanotube transistors.•The magnitude of this conductance change depends on the energization state of the mitochondria.•Compared to fluorescence, electrical measurements of membrane potential can provide higher time resolution and accuracy.We report label-free detection of single mitochondria with high sensitivity using nanoelectrodes. Measurements of the conductance of carbon nanotube transistors show discrete changes of conductance as individual mitochondria flow over the nanoelectrodes in a microfluidic channel. Altering the bioenergetic state of the mitochondria by adding metabolites to the flow buffer induces changes in the mitochondrial membrane potential detected by the nanoelectrodes. During the time when mitochondria are transiently passing over the nanoelectrodes, this (nano) technology is sensitive to fluctuations of the mitochondrial membrane potential with a resolution of 10 mV with temporal resolution of order milliseconds. Fluorescence based assays (in ideal, photon shot noise limited setups) are shown to be an order of magnitude less sensitive than this nano-electronic measurement technology. This opens a new window into the dynamics of an organelle critical to cellular function and fate.

Until recently, the dual roles of mitochondria in ATP production (bioenergetics) and apoptosis (cell life/death decision) were thought to be separate. New evidence points to a more intimate link between these two functions, mediated by the remodeling of the mitochondrial ultrastructure during apoptosis. While most of the key molecular players that regulate this process have been identified (primarily membrane proteins), the exact mechanisms by which they function are not yet understood. Because resistance to apoptosis is a hallmark of cancer, and because ultimately all chemotherapies are believed to result directly or indirectly in induction of apoptosis, a better understanding of the biophysical processes involved may lead to new avenues for therapy.

We report a two-step chemical vapor deposition growth method for rapid synthesis of isolated large-domain graphene. The key feature of the two-step growth method is to separate nucleation from growth, performing the nucleation in step one with a low carbon feedstock (methane) gas flow rate, and rapid growth in step two with a high flow rate. We find empirically that, even under the high flow rate conditions of step two, the nucleation density on the inside of the copper pocket used for growth is suppressed (preventing merging of domains into full films) until the graphene growing on the outside of the pocket merges into a full film, fully covering the outside. The mechanism for this suppression is believed to be related to oxygen-assisted passivation of nucleation sites, a decreased energetic barrier for edge-attachment growth, and diffusion of carbon through the copper bulk. These conditions enable us to finely tune the local carbon concentration on the inside surface for fast growth and minimum nucleation density and achieve a growth of 5 mm isolated graphene domains in under 5 h of total growth time, much faster than traditional one-step growth methods.

We apply polyelectrolyte multilayer films by consecutive alternate adsorption of positively charged polyallylamine hydrochloride and negatively charged sodium polystyrene sulfonate to the surface of graphene field effect transistors. Oscillations in the Dirac voltage shift with alternating positive and negative layers clearly demonstrate the electrostatic gating effect in this simple model system. A simple electrostatic model accounts well for the sign and magnitude of the Dirac voltage shift. Using this system, we are able to create p-type or n-type graphene at will. This model serves as the basis for understanding the mechanism of charged polymer sensing using graphene devices, a potentially technologically important application of graphene in areas such as DNA sequencing, biomarker assays for cancer detection, and other protein sensing applications.

The interaction of cell and organelle membranes (lipid bilayers) with nanoelectronics can enable new technologies to sense and measure electrophysiology in qualitatively new ways. To date, a variety of sensing devices have been demonstrated to measure membrane currents through macroscopic numbers of ion channels. However, nanoelectronic based sensing of single ion channel currents has been a challenge. Here, we report graphene-based field-effect transistors combined with supported lipid bilayers as a platform for measuring, for the first time, individual ion channel activity. We show that the supported lipid bilayers uniformly coat the single layer graphene surface, acting as a biomimetic barrier that insulates (both electrically and chemically) the graphene from the electrolyte environment. Upon introduction of pore-forming membrane proteins such as alamethicin and gramicidin A, current pulses are observed through the lipid bilayers from the graphene to the electrolyte, which charge the quantum capacitance of the graphene. This approach combines nanotechnology with electrophysiology to demonstrate qualitatively new ways of measuring ion channel currents.Keywords: biosensor; graphene; ion channel; lipid bilayer; transistor

Using nanofluidic channels in PDMS of cross section 500 nm × 2 μm, we demonstrate the trapping and interrogation of individual, isolated mitochondria. Fluorescence labeling demonstrates the immobilization of mitochondria at discrete locations along the channel. Interrogation of mitochondrial membrane potential with different potential sensitive dyes (JC-1 and TMRM) indicates the trapped mitochondria are vital in the respiration buffer. Fluctuations of the membrane potential can be observed at the single mitochondrial level. A variety of chemical challenges can be delivered to each individual mitochondrion in the nanofluidic system. As sample demonstrations, increases in the membrane potential are seen upon introduction of OXPHOS substrates into the nanofluidic channel. Introduction of Ca2+ into the nanochannels induces mitochondrial membrane permeabilization (MMP), leading to depolarization, observed at the single mitochondrial level. A variety of applications in cancer biology, stem cell biology, apoptosis studies, and high throughput functional metabolomics studies can be envisioned using this technology.

While the potential for high mobility printed semiconducting nanotube inks has been clear for over a decade, a myriad of scientific and technological issues has prevented commercialization and practical use. One of the most challenging scientific problems has been to understand the relationship between the pristine, individual nanotube mobility (known to be in the 10 000 cm2/V·s range) and the as-deposited random network mobility (recently demonstrated in the 100 cm2/V·s range). An additional significant scientific hurdle has been to understand, manage, and ultimately eliminate the effects of metallic nanotubes on the network performance, specifically the on/off ratio. Additional scientific progress is important in understanding the dependence of nanotube length, diameter, and density on device performance. Finally, the development of ink formulations that are of practical use in manufacturing is of paramount importance, especially with regard to drying time and uniformity, and ultimately, the issue of scalability and cost must be addressed. Many of these issues have recently been investigated from a phenomenological point of view, and a comprehensive understanding is beginning to emerge. In this paper, we present an overview of solution-based printed carbon nanotube devices and discuss long-term technology prospects. While significant technical challenges still remain, it is clear that the prospects for the use of nanotube ink in a myriad of systems is feasible given their unmatched mobility and compatibility with heterogeneous integration into a variety of applications in printed and flexible electronics.Keywords: circuit demonstration; mobility; nanotube network density; on/off ratio; radio frequency; random network; semiconducting carbon nanotube; solution-based deposition; thin film transistor

The mitochondrial membrane potential is used to generate and regulate energy in living systems, driving the conversion of ADP to ATP, regulating ion homeostasis, and controlling apoptosis, all central to human health and disease. Therefore, there is a need for tools to study its regulation in a controlled environment for potential clinical and scientific applications. For this aim, an on-chip tetraphenylphosphonium (TPP+) selective microelectrode sensor was constructed in a microfluidic environment. The concentration of isolated mitochondria (Heb7A) used in a membrane potential measurement was 0.3 ng µL−1, four orders of magnitude smaller than the concentration used in conventional assays (3 µg µL−1). In addition, the volume of the chamber (85 µL) is 2 orders of magnitude smaller than traditional experiments. As a demonstration, changes in the membrane potential are clearly measured in response to a barrage of well-known substrates and inhibitors of the electron transport chain. This general approach, which to date has not been demonstrated for study of mitochondrial function and bio-energetics in generally, can be instrumental in advancing the field of mitochondrial research and clinical applications by allowing high throughput studies of the regulation, dynamics, and statistical properties of the mitochondrial membrane potential in response to inhibitors and inducers of apoptosis in a controlled (microfluidic) chemical environment.

We present an overview of progress towards single-chip RFID solutions. To date heterogeneous integration has been appropriate for non-biological systems. However, for in-vivo sensors and even drug delivery systems, a small form factor is required. We discuss fundamental limits on the size of the form factor, the effect of the antenna, and propose a unified single-chip RFID solution appropriate for a broad range of biomedical in-vivo device applications, both current and future. Fundamental issues regarding the possibility of single cell RF radios to interface with biological function are discussed.

Here we present an easy one-step approach to pattern uniform catalyst lines for the growth of dense, aligned parallel arrays of single-walled carbon nanotubes (SWNTs) on quartz wafers by using photolithography or polydimethylsiloxane (PDMS) stamp microcontact printing (µCP). By directly doping an FeCl3/methanol solution into Shipley 1827 photoresist or polyvinylpyrrolidone (PVP), various catalyst lines can be well-patterned on a wafer scale. In addition, during the chemical vapor deposition (CVD) growth of SWNTs the polymer layers play a very important role in the formation of mono-dispersed nanoparticles. This universal and efficient method for the patterning growth of SWNTs arrays on a surface is compatible with the microelectronics industry, thus enabling of the fabrication highly integrated circuits of SWNTs.

We present phenomenological predictions for the cutoff frequency of carbon nanotube transistors. We also present predictions of the effects parasitic capacitances on AC nanotube transistor performance. The influence of quantum capacitance, kinetic inductance, and ballistic transport on the high-frequency properties of nanotube transistors is analyzed. We discuss the challenges of impedance matching for ac nano-electronics in general, and show how integrated nanosystems can solve this challenge. Our calculations show that carbon nano-electronics may be faster than conventional Si, SiGe, GaAs, or InP semiconductor technologies. We predict a cutoff frequency of 80 GHz/L, where L is the gate length in microns, opening up the possibility of a ballistic THz nanotube transistor.

By measuring the ac impedance, we measure for the first time the crossover from diffusive (ωτ<1) to ballistic (ωτ>1) transport as a function of frequency (dc to 5 GHz) in a dc contacted 2d electron gas in the low electric field limit, where τ is the momentum scattering time. The geometry is an “ungated HEMT”, meaning current flows through an ohmic contact into a 2d electron gas, laterally through the 2d electron gas, and out into a second ohmic contact; the 2d electron gas itself is not gated. At the measurement temperature (4.2 K), the low field mobility is 3.2 × 106 cm2/V s. We also measure for the first time the frequency dependent contact impedance in this ballistic limit.

Using gold electrodes lithographically fabricated onto microscope cover slips, DNA and proteins are interrogated both optically (through fluorescence) and electronically (through conductance measurements). Dielectrophoresis is used to position the DNA and proteins at well-defined positions on a chip. Quadrupole electrode geometries are investigated with gaps ranging from 3 to 100 μm; field strengths are typically 106 V/m. Twenty nanometer latex beads are also manipulated. The electrical resistance of the electronically manipulated DNA and proteins is measured to be larger than 40 MΩ under the experimental conditions used. The technique of simultaneously measuring resistance while using dielectrophoresis to trap nanoscale objects should find broad applicability.