Scalable Nanogap Sensors for Non-Redox Enzyme Assays.

Clinical diagnostic assays that monitor redox enzyme activity are widely used in small, low-cost readout devices for point-of-care monitoring (e.g., a glucometer); however, monitoring non-redox enzymes in real-time using compact electronic devices remains a challenge. We address this problem by using a highly scalable nanogap sensor array to observe electrochemical signals generated by a model non-redox enzyme system, the DNA polymerase-catalyzed incorporation of four modified, redox-tagged nucleotides. Using deoxynucleoside triphosphates (dNTPs) tagged with para-aminophenyl monophosphate (pAPP) to form pAP-deoxyribonucleoside tetra-phosphates (AP-dN4Ps), incorporation of the nucleotide analogs by DNA polymerase results in the release of redox inactive pAP-triphosphates (pAPP3) that are converted to redox active small molecules para-aminophenol (pAP) in the presence of phosphatase. In this work, cyclic enzymatic reactions that generated many copies of pAP at each base incorporation site of a DNA template in combination with the highly confined nature of the planar nanogap transducers ( z = 50 nm) produced electrochemical signals that were amplified up to 100,000×. We observed that the maximum signal level and amplification level were dependent on a combination of factors including the base structure of the incorporated nucleotide analogs, nanogap electrode materials, and electrode surface coating. In addition, electrochemical signal amplification by redox cycling in the nanogap is independent of the in-plane geometry of the transducer, thus allowing the nanogap sensors to be highly scalable. Finally, when the DNA template concentration was constrained, the DNA polymerase assay exhibited different zero-order reaction kinetics for each type of base incorporation reaction, resolving the closely related nucleotide analogs.

Mechanical model of vertical nanowire cell penetration.

Direct access into cells' interiors is essential for biomolecular delivery, gene transfection, and electrical recordings yet is challenging due to the cell membrane barrier. Recently, molecular delivery using vertical nanowires (NWs) has been demonstrated for introducing biomolecules into a large number of cells in parallel. However, the microscopic understanding of how and when the nanowires penetrate cell membranes is still lacking, and the degree to which actual membrane penetration occurs is controversial. Here we present results from a mechanical continuum model of elastic cell membrane penetration through two mechanisms, namely through "impaling" as cells land onto a bed of nanowires, and through "adhesion-mediated" penetration, which occurs as cells spread on the substrate and generate adhesion force. Our results reveal that penetration is much more effective through the adhesion mechanism, with NW geometry and cell stiffness being critically important. Stiffer cells have higher penetration efficiency, but are more sensitive to NW geometry. These results provide a guide to designing nanowires for applications in cell membrane penetration.

Tuning the built-in electric field in ferroelectric Pb(Zr(0.2)Ti(0.8))O3 films for long-term stability of single-digit nanometer inverted domains.

The emergence of new technologies, such as whole genome sequencing systems, which generate a large amount of data, is requiring ultrahigh storage capacities. Due to their compactness and low power consumption, probe-based memory devices using Pb(Zr(0.2)Ti(0.8))O(3) (PZT) ferroelectric films are the ideal candidate for such applications where portability is desired. To achieve ultrahigh (>1 Tbit/in(2)) storage densities, sub-10 nm inverted domains are required. However, such domains remain unstable and can invert back to their original polarization due to the effects of an antiparallel built-in electric field in the PZT film, domain-wall, and depolarization energies. Here, we show that the built-in electric-field can be tuned and suppressed by repetitive hydrogen and oxygen plasma treatments. Such treatments trigger reversible Pb reduction/oxidation activity, which alters the electrochemistry of the Pb overlayer and compensates for charges induced by the Pb vacancies. This tuning mechanism is used to demonstrate the writing of stable and equal size sub-4 nm domains in both up- and down-polarized PZT films, corresponding to eight inverted unit-cells. The bit sizes recorded here are the smallest ever achieved, which correspond to potential 60 Tbit/in(2) data storage densities.

An ultraclean tip-wear reduction scheme for ultrahigh density scanning probe-based data storage.

Probe-based memory devices using ferroelectric media have the potential to achieve ultrahigh data-storage densities under high write-read speeds. However, the high-speed scanning operations over a device lifetime of 5-10 years, which corresponds to a probe tip sliding distance of 5-10 km, can cause the probe tip to mechanically wear, critically affecting its write-read resolution. Here, we show that the long distance tip-wear endurance issue can be resolved by introducing a thin water layer at the tip-media interface-thin enough to form a liquid crystal. By modulating the force at the tip-surface contact, this water crystal layer can act as a viscoelastic material which reduces the stress level on atomic bonds taking part in the wear process. Under our optimized environment, a platinum-iridium probe tip can retain its write-read resolution over 5 km of sliding at a 5 mm/s velocity on a smooth ferroelectric film. We also demonstrate a 3.6 Tbit/inch(2) storage density over a 1 × 1 µm(2) area, which is the highest density ever written on ferroelectric films over such a large area.