James R. Heath

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Name: Heath, James R.; James R. Heath

Organization: Caltech Chemistry , USA

Department: Division of Chemistry and Chemical Engineering

Title: (PhD)

TOPICS

Physical Chemistry

Analytical Chemistry

Chemicals
References

Scanning Tunneling Microscopy Characterization of the Electrical Properties of Wrinkles in Exfoliated Graphene Monolayers

Co-reporter:Ke Xu, Peigen Cao and James R. Heath

Nano Letters December 9, 2009 Volume 9(Issue 12) pp:4446-4451

Publication Date(Web):October 23, 2009

DOI:10.1021/nl902729p

We report on the scanning tunneling microscopy study of a new class of corrugations in exfoliated monolayer graphene sheets, that is, wrinkles ∼10 nm in width and ∼3 nm in height. We found such corrugations to be ubiquitous in graphene and have distinctly different properties when compared to other regions of graphene. In particular, a “three-for-six” triangular pattern of atoms is exclusively and consistently observed on wrinkles, suggesting the local curvature of the wrinkle provides a sufficient perturbation to break the 6-fold symmetry of the graphene lattice. Through scanning tunneling spectroscopy, we further demonstrate that the wrinkles have lower electrical conductance and are characterized by the presence of midgap states, which is in agreement with recent theoretical predictions. The observed wrinkles are likely important for understanding the electrical properties of graphene.

Supramolecular Probes for Assessing Glutamine Uptake Enable Semi-Quantitative Metabolic Models in Single Cells

Co-reporter:Min Xue; Wei Wei; Yapeng Su; Dazy Johnson

Journal of the American Chemical Society 2016 Volume 138(Issue 9) pp:3085-3093

Publication Date(Web):February 26, 2016

DOI:10.1021/jacs.5b12187

We describe a supramolecular surface competition assay for quantifying glutamine uptake from single cells. Cy3-labeled cyclodextrins were immobilized on a glass surface as a supramolecular host/FRET donor, and adamantane-BHQ2 conjugates were employed as the guest/quencher. An adamantane-labeled glutamine analog was selected through screening a library of compounds and validated by cell uptake experiments. When integrated onto a single cell barcode chip with a multiplex panel of 15 other metabolites, associated metabolic enzymes, and phosphoproteins, the resultant data provided input for a steady-state model that describes energy potential in single cells and correlates that potential with receptor tyrosine kinase signaling. We utilize this integrated assay to interrogate a dose-dependent response of model brain cancer cells to EGFR inhibition. We find that low-dose (1 μM erlotinib) drugging actually increases cellular energy potential even as glucose uptake and phosphoprotein signaling is repressed. We also identify new interactions between phosphoprotein signaling and cellular energy processes that may help explain the facile resistance exhibited by certain cancer patients to EGFR inhibitors.

Intercellular signaling through secreted proteins induces free-energy gradient-directed cell movement

Co-reporter:Nataly Kravchenko-Balasha;Young Shik Shin;R. D. Levine;Alex Sutherland

PNAS 2016 Volume 113 (Issue 20 ) pp:5520-5525

Publication Date(Web):2016-05-17

DOI:10.1073/pnas.1602171113

Controlling cell migration is important in tissue engineering and medicine. Cell motility depends on factors such as nutrient concentration gradients and soluble factor signaling. In particular, cell–cell signaling can depend on cell–cell separation distance and can influence cellular arrangements in bulk cultures. Here, we seek a physical-based approach, which identifies a potential governed by cell–cell signaling that induces a directed cell–cell motion. A single-cell barcode chip (SCBC) was used to experimentally interrogate secreted proteins in hundreds of isolated glioblastoma brain cancer cell pairs and to monitor their relative motions over time. We used these trajectories to identify a range of cell–cell separation distances where the signaling was most stable. We then used a thermodynamics-motivated analysis of secreted protein levels to characterize free-energy changes for different cell–cell distances. We show that glioblastoma cell–cell movement can be described as Brownian motion biased by cell–cell potential. To demonstrate that the free-energy potential as determined by the signaling is the driver of motion, we inhibited two proteins most involved in maintaining the free-energy gradient. Following inhibition, cell pairs showed an essentially random Brownian motion, similar to the case for untreated, isolated single cells.

A Thermodynamic-Based Interpretation of Protein Expression Heterogeneity in Different Glioblastoma Multiforme Tumors Identifies Tumor-Specific Unbalanced Processes

Co-reporter:Nataly Kravchenko-Balasha, Hannah Johnson, Forest M. White, James R. Heath, and R. D. Levine

The Journal of Physical Chemistry B 2016 Volume 120(Issue 26) pp:5990-5997

Publication Date(Web):April 1, 2016

DOI:10.1021/acs.jpcb.6b01692

We describe a thermodynamic-motivated, information theoretic analysis of proteomic data collected from a series of 8 glioblastoma multiforme (GBM) tumors. GBMs are considered here as prototypes of heterogeneous cancers. That heterogeneity is viewed here as manifesting in different unbalanced biological processes that are associated with thermodynamic-like constraints. The analysis yields a molecular description of a stable steady state that is common across all tumors. It also resolves molecular descriptions of unbalanced processes that are shared by several tumors, such as hyperactivated phosphoprotein signaling networks. Further, it resolves unbalanced processes that provide unique classifiers of tumor subgroups. The results of the theoretical interpretation are compared against those of statistical multivariate methods and are shown to provide a superior level of resolution for identifying unbalanced processes in GBM tumors. The identification of specific constraints for each GBM tumor suggests tumor-specific combination therapies that may reverse this imbalance.

The Influence of Water on the Optical Properties of Single-Layer Molybdenum Disulfide

Co-reporter:Joseph O. Varghese;Peter Agbo;Alexer M. Sutherl;Victor W. Brar;George R. Rossman;Harry B. Gray

Advanced Materials 2015 Volume 27( Issue 17) pp:2734-2740

Publication Date(Web):

DOI:10.1002/adma.201500555

Chemical Methods for the Simultaneous Quantitation of Metabolites and Proteins from Single Cells

Co-reporter:Min Xue; Wei Wei; Yapeng Su; Jungwoo Kim; Young Shik Shin; Wilson X. Mai; David A. Nathanson

Journal of the American Chemical Society 2015 Volume 137(Issue 12) pp:4066-4069

Publication Date(Web):March 19, 2015

DOI:10.1021/jacs.5b00944

We describe chemical approaches for integrated metabolic and proteomic assays from single cells. Quantitative assays for intracellular metabolites, including glucose uptake and three other species, are designed as surface-competitive binding assays with fluorescence readouts. This enables integration into a microarray format with functional protein immunoassays, all of which are incorporated into the microchambers of a single-cell barcode chip (SCBC). By using the SCBC, we interrogate the response of human-derived glioblastoma cancer cells to epidermal growth factor receptor inhibition. We report, for the first time, on both the intercellular metabolic heterogeneity as well as the baseline and drug-induced changes in the metabolite–phosphoprotein correlation network.

Nanotechnologies for biomedical science and translational medicine

Co-reporter:James R. Heath

PNAS 2015 Volume 112 (Issue 47 ) pp:14436-14443

Publication Date(Web):2015-11-24

DOI:10.1073/pnas.1515202112

In 2000 the United States launched the National Nanotechnology Initiative and, along with it, a well-defined set of goals for nanomedicine. This Perspective looks back at the progress made toward those goals, within the context of the changing landscape in biomedicine that has occurred over the past 15 years, and considers advances that are likely to occur during the next decade. In particular, nanotechnologies for health-related genomics and single-cell biology, inorganic and organic nanoparticles for biomedicine, and wearable nanotechnologies for wellness monitoring are briefly covered.

Epitope Targeting of Tertiary Protein Structure Enables Target-Guided Synthesis of a Potent In-Cell Inhibitor of Botulinum Neurotoxin

Co-reporter:Blake Farrow;Michelle Wong;Jacquie Malette;Dr. Bert Lai;Dr. Kaycie M. Deyle;Dr. Samir Das;Dr. Arundhati Nag;Dr. Heather D. Agnew; James R. Heath

Angewandte Chemie International Edition 2015 Volume 54( Issue 24) pp:7114-7119

Publication Date(Web):

DOI:10.1002/anie.201502451

Abstract

Botulinum neurotoxin (BoNT) serotype A is the most lethal known toxin and has an occluded structure, which prevents direct inhibition of its active site before it enters the cytosol. Target-guided synthesis by in situ click chemistry is combined with synthetic epitope targeting to exploit the tertiary structure of the BoNT protein as a landscape for assembling a competitive inhibitor. A substrate-mimicking peptide macrocycle is used as a direct inhibitor of BoNT. An epitope-targeting in situ click screen is utilized to identify a second peptide macrocycle ligand that binds to an epitope that, in the folded BoNT structure, is active-site-adjacent. A second in situ click screen identifies a molecular bridge between the two macrocycles. The resulting divalent inhibitor exhibits an in vitro inhibition constant of 165 pM against the BoNT/A catalytic chain. The inhibitor is carried into cells by the intact holotoxin, and demonstrates protection and rescue of BoNT intoxication in a human neuron model.

A General Synthetic Approach for Designing Epitope Targeted Macrocyclic Peptide Ligands

Co-reporter:Dr. Samir Das;Dr. Arundhati Nag;JingXin Liang;Dr. David N. Bunck;Dr. Aiko Umeda;Blake Farrow;Matthew B. Coppock;Deborah A. Sarkes;Amethist S. Finch;Heather D. Agnew;Suresh Pitram;Bert Lai;Mary Beth Yu;Dr. A. Katrine Museth;Dr. Kaycie M. Deyle;Bianca Lepe;Frances P. Rodriguez-Rivera;Amy McCarthy;Belen Alvarez-Villalonga;Ann Chen;John Heath;Dimitra N. Stratis-Cullum; James R. Heath

Angewandte Chemie International Edition 2015 Volume 54( Issue 45) pp:13219-13224

Publication Date(Web):

DOI:10.1002/anie.201505243

Abstract

We describe a general synthetic strategy for developing high-affinity peptide binders against specific epitopes of challenging protein biomarkers. The epitope of interest is synthesized as a polypeptide, with a detection biotin tag and a strategically placed azide (or alkyne) presenting amino acid. This synthetic epitope (SynEp) is incubated with a library of complementary alkyne or azide presenting peptides. Library elements that bind the SynEp in the correct orientation undergo the Huisgen cycloaddition, and are covalently linked to the SynEp. Hit peptides are tested against the full-length protein to identify the best binder. We describe development of epitope-targeted linear or macrocycle peptide ligands against 12 different diagnostic or therapeutic analytes. The general epitope targeting capability for these low molecular weight synthetic ligands enables a range of therapeutic and diagnostic applications, similar to those of monoclonal antibodies.

Epitope Targeting of Tertiary Protein Structure Enables Target-Guided Synthesis of a Potent In-Cell Inhibitor of Botulinum Neurotoxin

Co-reporter:Blake Farrow;Michelle Wong;Jacquie Malette;Dr. Bert Lai;Dr. Kaycie M. Deyle;Dr. Samir Das;Dr. Arundhati Nag;Dr. Heather D. Agnew; James R. Heath

Angewandte Chemie 2015 Volume 127( Issue 24) pp:7220-7225

Publication Date(Web):

DOI:10.1002/ange.201502451

Abstract

A General Synthetic Approach for Designing Epitope Targeted Macrocyclic Peptide Ligands

Angewandte Chemie 2015 Volume 127( Issue 45) pp:13417-13422

Publication Date(Web):

DOI:10.1002/ange.201505243

Abstract

Glioblastoma cellular architectures are predicted through the characterization of two-cell interactions

Co-reporter:Nataly Kravchenko-Balasha;Francoise Remacle;Jun Wang;R. D. Levine

PNAS 2014 Volume 111 (Issue 17 ) pp:6521-6526

Publication Date(Web):2014-04-29

DOI:10.1073/pnas.1404462111

To understand how pairwise cellular interactions influence cellular architectures, we measured the levels of functional proteins associated with EGF receptor (EGFR) signaling in pairs of U87EGFR variant III oncogene receptor cells (U87EGFRvIII) at varying cell separations. Using a thermodynamics-derived approach we analyzed the cell-separation dependence of the signaling stability, and identified that the stable steady state of EGFR signaling exists when two U87EGFRvIII cells are separated by 80–100 μm. This distance range was verified as the characteristic intercellular separation within bulk cell cultures. EGFR protein network signaling coordination for the U87EGFRvIII system was lowest at the stable state and most similar to isolated cell signaling. Measurements of cultures of less tumorigenic U87PTEN cells were then used to correctly predict that stable EGFR signaling occurs for those cells at smaller cell–cell separations. The intimate relationship between functional protein levels and cellular architectures explains the scattered nature of U87EGFRvIII cells relative to U87PTEN cells in glioblastoma multiforme tumors.

A Chemically Synthesized Capture Agent Enables the Selective, Sensitive, and Robust Electrochemical Detection of Anthrax Protective Antigen

Co-reporter:Blake Farrow, Sung A Hong, Errika C. Romero, Bert Lai, Matthew B. Coppock, Kaycie M. Deyle, Amethist S. Finch, Dimitra N. Stratis-Cullum, Heather D. Agnew, Sung Yang, and James R. Heath

ACS Nano 2013 Volume 7(Issue 10) pp:9452

Publication Date(Web):September 24, 2013

DOI:10.1021/nn404296k

We report on a robust and sensitive approach for detecting protective antigen (PA) exotoxin from Bacillus anthracis in complex media. A peptide-based capture agent against PA was developed by improving a bacteria display-developed peptide into a highly selective biligand through in situ click screening against a large, chemically synthesized peptide library. This biligand was coupled with an electrochemical enzyme-linked immunosorbent assay utilizing nanostructured gold electrodes. The resultant assay yielded a limit of detection of PA of 170 pg/mL (2.1 pM) in buffer, with minimal sensitivity reduction in 1% serum. The powdered capture agent could be stably stored for several days at 65 °C, and the full electrochemical biosensor showed no loss of performance after extended storage at 40 °C. The engineered stability and specificity of this assay should be extendable to other cases in which biomolecular detection in demanding environments is required.Keywords: anthrax; biosensing; electrochemistry; ELISA; nanomaterial; pathogens; protein capture agents

Hypoxia induces a phase transition within a kinase signaling network in cancer cells

Co-reporter:Qihui Shi;Wei Wei;Francoise Remacle;David B. Shackelford;Lidong Qin;Paul S. Mischel;Young Shik Shin;R. D. Levine

PNAS 2013 Volume 110 (Issue 15 ) pp:E1352-E1360

Publication Date(Web):2013-04-09

DOI:10.1073/pnas.1303060110

Hypoxia is a near-universal feature of cancer, promoting glycolysis, cellular proliferation, and angiogenesis. The molecular mechanisms of hypoxic signaling have been intensively studied, but the impact of changes in oxygen partial pressure (pO2) on the state of signaling networks is less clear. In a glioblastoma multiforme (GBM) cancer cell model, we examined the response of signaling networks to targeted pathway inhibition between 21% and 1% pO2. We used a microchip technology that facilitates quantification of a panel of functional proteins from statistical numbers of single cells. We find that near 1.5% pO2, the signaling network associated with mammalian target of rapamycin (mTOR) complex 1 (mTORC1)—a critical component of hypoxic signaling and a compelling cancer drug target—is deregulated in a manner such that it will be unresponsive to mTOR kinase inhibitors near 1.5% pO2, but will respond at higher or lower pO2 values. These predictions were validated through experiments on bulk GBM cell line cultures and on neurosphere cultures of a human-origin GBM xenograft tumor. We attempt to understand this behavior through the use of a quantitative version of Le Chatelier’s principle, as well as through a steady-state kinetic model of protein interactions, both of which indicate that hypoxia can influence mTORC1 signaling as a switch. The Le Chatelier approach also indicates that this switch may be thought of as a type of phase transition. Our analysis indicates that certain biologically complex cell behaviors may be understood using fundamental, thermodynamics-motivated principles.

A Chemical Epitope-Targeting Strategy for Protein Capture Agents: The Serine 474 Epitope of the Kinase Akt2

Co-reporter:Dr. Arundhati Nag;Dr. Samir Das;Mary Beth Yu;Kaycie M. Deyle;Dr. Steven W. Millward; James R. Heath

Angewandte Chemie International Edition 2013 Volume 52( Issue 52) pp:13975-13979

Publication Date(Web):

DOI:10.1002/anie.201305882

A Chemical Epitope-Targeting Strategy for Protein Capture Agents: The Serine 474 Epitope of the Kinase Akt2

Co-reporter:Dr. Arundhati Nag;Dr. Samir Das;Mary Beth Yu;Kaycie M. Deyle;Dr. Steven W. Millward; James R. Heath

Angewandte Chemie 2013 Volume 125( Issue 52) pp:14225-14229

Publication Date(Web):

DOI:10.1002/ange.201305882

Visualizing Local Doping Effects of Individual Water Clusters on Gold(111)-Supported Graphene

Co-reporter:Peigen Cao, Joseph O. Varghese, Ke Xu, and James R. Heath

Nano Letters 2012 Volume 12(Issue 3) pp:1459-1463

Publication Date(Web):February 10, 2012

DOI:10.1021/nl2041673

The local charge carrier density of graphene can exhibit significant and highly localized variations that arise from the interaction between graphene and the local environment, such as adsorbed water, or a supporting substrate. However, it has been difficult to correlate such spatial variations with individual impurity sites. By trapping (under graphene) nanometer-sized water clusters on the atomically well-defined Au(111) substrate, we utilize scanning tunneling microscopy and spectroscopy to characterize the local doping influence of individual water clusters on graphene. We find that water clusters, predominantly nucleated at the atomic steps of Au(111), induce strong and highly localized electron doping in graphene. A positive correlation is observed between the water cluster size and the local doping level, in support of the recently proposed electrostatic-field-mediated doping mechanism. Our findings quantitatively demonstrate the importance of substrate-adsorbed water on the electronic properties of graphene.

Quantitating Cell–Cell Interaction Functions with Applications to Glioblastoma Multiforme Cancer Cells

Co-reporter:Jun Wang, Douglas Tham, Wei Wei, Young Shik Shin, Chao Ma, Habib Ahmad, Qihui Shi, Jenkan Yu, Raphael D. Levine, and James R. Heath

Nano Letters 2012 Volume 12(Issue 12) pp:6101-6106

Publication Date(Web):November 6, 2012

DOI:10.1021/nl302748q

We report on a method for quantitating the distance dependence of cell–cell interactions. We employ a microchip design that permits a multiplex, quantitative protein assay from statistical numbers of cell pairs, as a function of cell separation, with a 0.15 nL volume microchamber. We interrogate interactions between pairs of model brain cancer cells by assaying for six functional proteins associated with PI3k signaling. At short incubation times, cells do not appear to influence each other, regardless of cell separation. For 6 h incubation times, the cells exert an inhibiting influence on each other at short separations and a predominately activating influence at large separation. Protein-specific cell–cell interaction functions are extracted, and by assuming pairwise additivity of those interactions, the functions are shown to correctly predict the results from three-cell experiments carried out under the identical conditions.

Single-cell proteomic chip for profiling intracellular signaling pathways in single tumor cells

Co-reporter:Qihui Shi;Wei Wei;Lidong Qin;Rong Fan;Feng Geng;Deliang Guo;Young Shik Shin;Leroy Hood;Paul S. Mischel

PNAS 2012 Volume 109 (Issue 2 ) pp:

Publication Date(Web):2012-01-10

DOI:10.1073/pnas.1110865109

We describe a microchip designed to quantify the levels of a dozen cytoplasmic and membrane proteins from single cells. We use the platform to assess protein–protein interactions associated with the EGF-receptor-mediated PI3K signaling pathway. Single-cell sensitivity is achieved by isolating a defined number of cells (n = 0–5) in 2 nL volume chambers, each of which is patterned with two copies of a miniature antibody array. The cells are lysed on-chip, and the levels of released proteins are assayed using the antibody arrays. We investigate three isogenic cell lines representing the cancer glioblastoma multiforme, at the basal level, under EGF stimulation, and under erlotinib inhibition plus EGF stimulation. The measured protein abundances are consistent with previous work, and single-cell analysis uniquely reveals single-cell heterogeneity, and different types and strengths of protein–protein interactions. This platform helps provide a comprehensive picture of altered signal transduction networks in tumor cells and provides insight into the effect of targeted therapies on protein signaling networks.

The Microscopic Structure of Adsorbed Water on Hydrophobic Surfaces under Ambient Conditions

Co-reporter:Peigen Cao, Ke Xu, Joseph O. Varghese, and James R. Heath

Nano Letters 2011 Volume 11(Issue 12) pp:5581-5586

Publication Date(Web):November 3, 2011

DOI:10.1021/nl2036639

The interaction of water vapor with hydrophobic surfaces is poorly understood. We utilize graphene templating to preserve and visualize the microscopic structures of adsorbed water on hydrophobic surfaces. Three well-defined surfaces [H–Si(111), graphite, and functionalized mica] were investigated, and water was found to adsorb as nanodroplets (∼10–100 nm in size) on all three surfaces under ambient conditions. The adsorbed nanodroplets were closely associated with atomic-scale surface defects and step-edges and wetted all the hydrophobic substrates with contact angles <∼10°, resulting in total water adsorption that was similar to what is found for hydrophilic surfaces. These results point to the significant differences between surface processes at the atomic/nanometer scales and in the macroscopic world.

Iterative in Situ Click Chemistry Assembles a Branched Capture Agent and Allosteric Inhibitor for Akt1

Co-reporter:Steven W. Millward ; Ryan K. Henning ; Gabriel A. Kwong ; Suresh Pitram ; Heather D. Agnew ; Kaycie M. Deyle ; Arundhati Nag ; Jason Hein ; Su Seong Lee ; Jaehong Lim ; Jessica A. Pfeilsticker ; K. Barry Sharpless

Journal of the American Chemical Society 2011 Volume 133(Issue 45) pp:18280-18288

Publication Date(Web):September 30, 2011

DOI:10.1021/ja2064389

We describe the use of iterative in situ click chemistry to design an Akt-specific branched peptide triligand that is a drop-in replacement for monoclonal antibodies in multiple biochemical assays. Each peptide module in the branched structure makes unique contributions to affinity and/or specificity resulting in a 200 nM affinity ligand that efficiently immunoprecipitates Akt from cancer cell lysates and labels Akt in fixed cells. Our use of a small molecule to preinhibit Akt prior to screening resulted in low micromolar inhibitory potency and an allosteric mode of inhibition, which is evidenced through a series of competitive enzyme kinetic assays. To demonstrate the efficiency and selectivity of the protein-templated in situ click reaction, we developed a novel QPCR-based methodology that enabled a quantitative assessment of its yield. These results point to the potential for iterative in situ click chemistry to generate potent, synthetically accessible antibody replacements with novel inhibitory properties.

Atomic Force Microscopy Characterization of Room-Temperature Adlayers of Small Organic Molecules through Graphene Templating

Co-reporter:Peigen Cao ; Ke Xu ; Joseph O. Varghese

Journal of the American Chemical Society 2011 Volume 133(Issue 8) pp:2334-2337

Publication Date(Web):February 4, 2011

DOI:10.1021/ja108554p

We report on the use of graphene templating to investigate the room-temperature structure and dynamics of weakly bound adlayers at the interfaces between solids and vapors of small organic molecules. Monolayer graphene sheets are employed to preserve and template molecularly thin adlayers of tetrahydrofuran (THF) and cyclohexane on atomically flat mica substrates, thus permitting a structural characterization of the adlayers under ambient conditions through atomic force microscopy. We found the first two adlayers of both molecules adsorb in a layer-by-layer fashion, and atomically flat two-dimensional islands are observed for both the first and the second adlayers. THF adlayers form initially as rounded islands but, over a period of weeks, evolve into faceted islands, suggesting that the adlayers possess both liquid and solid properties at room temperature. Cyclohexane adlayers form crystal-like faceted islands and are immobile under the graphene template. The heights of the second adlayers of THF and cyclohexane are measured to be 0.44 ± 0.02 and 0.50 ± 0.02 nm, respectively, in good agreement with the layer thicknesses in the monoclinic crystal structure of THF and the Phase I “plastic crystal” structure of cyclohexane. The first adlayers appear slightly thinner for both molecules, indicative of interactions of the molecules with the mica substrate.

High-Density, Multiplexed Patterning of Cells at Single-Cell Resolution for Tissue Engineering and Other Applications

Co-reporter:Udi Vermesh;Ophir Vermesh;Jun Wang;Gabriel A. Kwong;Chao Ma;Kiwook Hwang; James R. Heath

Angewandte Chemie International Edition 2011 Volume 50( Issue 32) pp:7378-7380

Publication Date(Web):

DOI:10.1002/anie.201102249

High-Density, Multiplexed Patterning of Cells at Single-Cell Resolution for Tissue Engineering and Other Applications

Co-reporter:Udi Vermesh;Ophir Vermesh;Jun Wang;Gabriel A. Kwong;Chao Ma;Kiwook Hwang; James R. Heath

Angewandte Chemie 2011 Volume 123( Issue 32) pp:7516-7518

Publication Date(Web):

DOI:10.1002/ange.201102249

High performance ring oscillators from 10-nm wide silicon nanowire field-effect transistors

Co-reporter:Ruo-Gu Huang;Douglas Tham;Dunwei Wang

Nano Research 2011 Volume 4( Issue 10) pp:1005-1012

Publication Date(Web):2011 October

DOI:10.1007/s12274-011-0157-2

We explore 10-nm wide Si nanowire (SiNW) field-effect transistors (FETs) for logic applications, via the fabrication and testing of SiNW-based ring oscillators. We report on SiNW surface treatments and dielectric annealing, for producing SiNW FETs that exhibit high performance in terms of large on/off-state current ratio (∼108), low drain-induced barrier lowering (∼30 mV) and low subthreshold swing (∼80 mV/decade). The performance of inverter and ring-oscillator circuits fabricated from these nanowire FETs are also explored. The inverter demonstrates the highest voltage gain (∼148) reported for a SiNW-based NOT gate, and the ring oscillator exhibits near rail-to-rail oscillation centered at 13.4 MHz. The static and dynamic characteristics of these NW devices indicate that these SiNW-based FET circuits are excellent candidates for various high-performance nanoelectronic applications. Open image in new window

Batch Fabrication of High-Performance Planar Patch-Clamp Devices in Quartz

Co-reporter:John M. Nagarah;Eunsu Paek;Yi Luo;Pin Wang;Gyeong S. Hwang

Advanced Materials 2010 Volume 22( Issue 41) pp:4622-4627

Publication Date(Web):

DOI:10.1002/adma.201001793

Ultradense, Deep Subwavelength Nanowire Array Photovoltaics As Engineered Optical Thin Films

Co-reporter:Douglas Tham and James R. Heath

Nano Letters 2010 Volume 10(Issue 11) pp:4429-4434

Publication Date(Web):October 8, 2010

DOI:10.1021/nl102199b

A photovoltaic device comprised of an array of 20 nm wide, 32 nm pitch array of silicon nanowires is modeled as an optical material. The nanowire array (NWA) has characteristic device features that are deep in the subwavelength regime for light, which permits a number of simplifying approximations. Using photocurrent measurements as a probe of the absorptance, we show that the NWA optical properties can be accurately modeled with rigorous coupled-wave analysis. The densely structured NWAs behave as homogeneous birefringent materials into the ultraviolet with effective optical properties that are accurately modeled using the dielectric functions of bulk Si and SiO2, coupled with a physical model for the NWA derived from ellipsometry and transmission electron microscopy.

Achieving the Theoretical Depairing Current Limit in Superconducting Nanomesh Films

Co-reporter:Ke Xu, Peigen Cao, and James R. Heath

Nano Letters 2010 Volume 10(Issue 10) pp:4206-4210

Publication Date(Web):August 25, 2010

DOI:10.1021/nl102584j

We show the theoretical depairing current limit can be achieved in a robust fashion in highly ordered superconductor nanomesh films having spatial periodicities smaller than both the superconducting coherence length and the magnetic penetration depth. For a niobium nanomesh film with 34 nm spatial periodicity, the experimental critical current density is enhanced by more than 17 times over the continuous film and is in good agreement with the depairing limit over the entire measured temperature range. The nanomesh superconductors are also less susceptible to thermal fluctuations when compared to nanowire superconductors. Tc values similar to the bulk film are achieved, and the nanomeshes are capable of retaining superconductivity to higher fields relative to the bulk. In addition, periodic oscillations in Tc are observed as a function of field, reflecting the highly ordered nanomesh structure.

A self-powered, one-step chip for rapid, quantitative and multiplexed detection of proteins from pinpricks of whole blood

Co-reporter:Jun Wang, Habib Ahmad, Chao Ma, Qihui Shi, Ophir Vermesh, Udi Vermesh and James Heath

Lab on a Chip 2010 vol. 10(Issue 22) pp:3157-3162

Publication Date(Web):06 Oct 2010

DOI:10.1039/C0LC00132E

We describe an automated, self-powered chip based on lateral flow immunoassay for rapid, quantitative, and multiplex protein detection from pinpricks of whole blood. The device incorporates on-chip purification of blood plasma by employing inertial forces to focus blood cells away from the assay surface, where plasma proteins are captured and detected on antibody “barcode” arrays. Power is supplied from the capillary action of a piece of adsorbent paper, and sequentially drives, over a 40 minute period, the four steps required to capture serum proteins and then develop a multiplex immunoassay. An 11 protein panel is assayed from whole blood, with high sensitivity and high reproducibility. This inexpensive, self-contained, and easy to operate chip provides a useful platform for point-of-care diagnoses, particularly in resource-limited settings.

Accurate MALDI-TOF/TOF Sequencing of One-Bead−One-Compound Peptide Libraries with Application to the Identification of Multiligand Protein Affinity Agents Using in Situ Click Chemistry Screening

Co-reporter:Su Seong Lee, Jaehong Lim, Sylvia Tan, Junhoe Cha, Shi Yun Yeo, Heather D. Agnew and James R. Heath

Analytical Chemistry 2010 Volume 82(Issue 2) pp:672

Publication Date(Web):December 14, 2009

DOI:10.1021/ac902195y

Combinatorial one-bead−one-compound (OBOC) peptide libraries are widely used for affinity screening, and the sequencing of peptides from hit beads is a key step in the process. For rapid sequencing, CNBr cleavage of the peptides from the beads, followed by de novo sequencing by MALDI-TOF/TOF, is explored. We report on a semiautomated sequencing algorithm and validate it through comparison against Edman degradation sequencing. The initial 44% sequencing success rate of the standard de novo sequencing software was improved to nearly 100%. The sequencing algorithm incorporates existing knowledge of amino acid chemistry and a new strategy for differentiating isobaric amino acids. We tested the algorithm by using MALDI-TOF/TOF to identify a peptide biligand affinity agent against the protein bovine carbonic anhydrase II, starting from comprehensive one-bead−one-compound peptide libraries comprised of non-natural and artificial amino acid components and using the strategy of in situ click/OBOC library screening.

Chemistries for Patterning Robust DNA MicroBarcodes Enable Multiplex Assays of Cytoplasm Proteins from Single Cancer Cells

Co-reporter:Young Shik Shin;Habib Ahmad;Dr. Qihui Shi;Dr. Hyungjun Kim;Dr. Tod A. Pascal; Rong Fan; William A. Goddard III; James R. Heath

ChemPhysChem 2010 Volume 11( Issue 14) pp:3063-3069

Publication Date(Web):

DOI:10.1002/cphc.201000528

Graphene Visualizes the First Water Adlayers on Mica at Ambient Conditions

Co-reporter:Ke Xu;Peigen Cao

Science 2010 Vol 329(5996) pp:1188-1191

Publication Date(Web):03 Sep 2010

DOI:10.1126/science.1192907

Scanning Tunneling Microscopy Characterization of the Electrical Properties of Wrinkles in Exfoliated Graphene Monolayers

Co-reporter:Ke Xu, Peigen Cao and James R. Heath

Nano Letters 2009 Volume 9(Issue 12) pp:4446-4451

Publication Date(Web):October 23, 2009

DOI:10.1021/nl902729p

Self-powered microfluidic chips for multiplexed protein assays from whole blood

Co-reporter:Lidong Qin, Ophir Vermesh, Qihui Shi and James R. Heath

Lab on a Chip 2009 vol. 9(Issue 14) pp:2016-2020

Publication Date(Web):16 Apr 2009

DOI:10.1039/B821247C

We report herein on a self-powered, self-contained microfluidic-based chip designed to separate plasma from whole blood, and then execute an assay of a multiplexed panel of plasma biomarker proteins. The power source is based upon a chemical reaction that is catalytically triggered by the push of a button on the chip. We demonstrate assays of a dozen blood-based protein biomarkers using this automated, self-contained device. This platform can potentially permit high throughput, accurate, multiplexed blood diagnostic measurements in remote locations and by minimally trained individuals.

Iterative In Situ Click Chemistry Creates Antibody-like Protein-Capture Agents

Co-reporter:HeatherD. Agnew;RosemaryD. Rohde;StevenW. Millward Dr.;Arundhati Nag;Woon-Seok Yeo Dr.;JasonE. Hein Dr.;SureshM. Pitram Dr.;AbdulAhad Tariq;VanessaM. Burns;RussellJ. Krom;ValeryV. Fokin ;K.Barry Sharpless ;JamesR. Heath

Angewandte Chemie International Edition 2009 Volume 48( Issue 27) pp:4944-4948

Publication Date(Web):

DOI:10.1002/anie.200900488

Iterative In Situ Click Chemistry Creates Antibody-like Protein-Capture Agents

Angewandte Chemie 2009 Volume 121( Issue 27) pp:5044-5048

Publication Date(Web):

DOI:10.1002/ange.200900488

Superlattice Nanowire Pattern Transfer (SNAP)

Co-reporter:James R. Heath

Accounts of Chemical Research 2008 Volume 41(Issue 12) pp:1609

Publication Date(Web):July 4, 2008

DOI:10.1021/ar800015y

During the past 15 years or so, nanowires (NWs) have emerged as a new and distinct class of materials. Their novel structural and physical properties separate them from wires that can be prepared using the standard methods for manufacturing electronics. NW-based applications that range from traditional electronic devices (logic and memory) to novel biomolecular and chemical sensors, thermoelectric materials, and optoelectronic devices, all have appeared during the past few years. From a fundamental perspective, NWs provide a route toward the investigation of new physics in confined dimensions. Perhaps the most familiar fabrication method is the vapor−liquid−solid (VLS) growth technique, which produces semiconductor nanowires as bulk materials. However, other fabrication methods exist and have their own advantages. In this Account, I review a particular class of NWs produced by an alternative method called superlattice nanowire pattern transfer (SNAP). The SNAP method is distinct from other nanowire preparation methods in several ways. It can produce large NW arrays from virtually any thin-film material, including metals, insulators, and semiconductors. The dimensions of the NWs can be controlled with near-atomic precision, and NW widths and spacings can be as small as a few nanometers. In addition, SNAP is almost fully compatible with more traditional methods for manufacturing electronics. The motivation behind the development of SNAP was to have a general nanofabrication method for preparing electronics-grade circuitry, but one that would operate at macromolecular dimensions and with access to a broad materials set. Thus, electronics applications, including novel demultiplexing architectures; large-scale, ultrahigh-density memory circuits; and complementary symmetry nanowire logic circuits, have served as drivers for developing various aspects of the SNAP method. Some of that work is reviewed here. As the SNAP method has evolved into a robust nanofabrication method, it has become an enabling tool for the investigation of new physics. In particular, the application of SNAP toward understanding heat transport in low-dimensional systems is discussed. This work has led to the surprising discovery that Si NWs can serve as highly efficient thermoelectric materials. Finally, we turn toward the application of SNAP to the investigation of quasi-one-dimensional (quasi-1D) superconducting physics in extremely high aspect ratio Nb NWs.

Rapid Microwave-Assisted CNBr Cleavage of Bead-Bound Peptides

Co-reporter:Su Seong Lee, Jaehong Lim, Junhoe Cha, Sylvia Tan and James R. Heath

ACS Combinatorial Science 2008 Volume 10(Issue 6) pp:807

Publication Date(Web):September 24, 2008

DOI:10.1021/cc800113d

Complementary Symmetry Nanowire Logic Circuits: Experimental Demonstrations and in Silico Optimizations

Co-reporter:Bonnie A. Sheriff, Dunwei Wang, James R. Heath and Juanita N. Kurtin

ACS Nano 2008 Volume 2(Issue 9) pp:1789

Publication Date(Web):August 12, 2008

DOI:10.1021/nn800025q

Complementary symmetry (CS) Boolean logic utilizes both p- and n-type field-effect transistors (FETs) so that an input logic voltage signal will turn one or more p- or n-type FETs on, while turning an equal number of n- or p-type FETs off. The voltage powering the circuit is prevented from having a direct pathway to ground, making the circuit energy efficient. CS circuits are thus attractive for nanowire logic, although they are challenging to implement. CS logic requires a relatively large number of FETs per logic gate, the output logic levels must be fully restored to the input logic voltage level, and the logic gates must exhibit high gain and robust noise margins. We report on CS logic circuits constructed from arrays of 16 nm wide silicon nanowires. Gates up to a complexity of an XOR gate (6 p-FETs and 6 n-FETs) containing multiple nanowires per transistor exhibit signal restoration and can drive other logic gates, implying that large scale logic can be implemented using nanowires. In silico modeling of CS inverters, using experimentally derived look-up tables of individual FET properties, is utilized to provide feedback for optimizing the device fabrication process. Based upon this feedback, CS inverters with a gain approaching 50 and robust noise margins are demonstrated. Single nanowire-based logic gates are also demonstrated, but are found to exhibit significant device-to-device fluctuations.Keywords: circuit simulations; complementary circuits; field effect transistors; nanotechnology; nanowire

Silicon nanowires as efficient thermoelectric materials

Co-reporter:Akram I. Boukai, Yuri Bunimovich, Jamil Tahir-Kheli, Jen-Kan Yu, William A. Goddard III & James R. Heath

Nature 2008 451(7175) pp:168

Publication Date(Web):2008-01-10

DOI:10.1038/nature06458

Thermoelectric materials interconvert thermal gradients and electric fields for power generation or for refrigeration1, 2. Thermoelectrics currently find only niche applications because of their limited efficiency, which is measured by the dimensionless parameter ZT—a function of the Seebeck coefficient or thermoelectric power, and of the electrical and thermal conductivities. Maximizing ZT is challenging because optimizing one physical parameter often adversely affects another3. Several groups have achieved significant improvements in ZT through multi-component nanostructured thermoelectrics4, 5, 6, such as Bi2Te3/Sb2Te3 thin-film superlattices, or embedded PbSeTe quantum dot superlattices. Here we report efficient thermoelectric performance from the single-component system of silicon nanowires for cross-sectional areas of 10 nm × 20 nm and 20 nm × 20 nm. By varying the nanowire size and impurity doping levels, ZT values representing an approximately 100-fold improvement over bulk Si are achieved over a broad temperature range, including ZT ≈ 1 at 200 K. Independent measurements of the Seebeck coefficient, the electrical conductivity and the thermal conductivity, combined with theory, indicate that the improved efficiency originates from phonon effects. These results are expected to apply to other classes of semiconductor nanomaterials.

A One-Pot Synthesis of Constitutionally Unsymmetrical Rotaxanes Using Sequential CuI-Catalyzed AzideAlkyne Cycloadditions

Co-reporter:JasonM. Spruell;WilliamR. Dichtel Dr.;JamesR. Heath Dr.;J.Fraser Stoddart Dr.

Chemistry - A European Journal 2008 Volume 14( Issue 14) pp:4168-4177

Publication Date(Web):

DOI:10.1002/chem.200800067

Abstract

A one-pot sequential Cu^I-catalyzed azide–alkyne cycloaddition (CuAAC) strategy is presented for the synthesis of constitutionally unsymmetrical cyclobis(paraquat-p-phenylene)-based rotaxanes in good yields from simple starting materials. The methodology consists of performing multiple CuAAC reactions to stopper a pseudorotaxane in a stepwise manner, the order of which is controlled through silyl-protection and Ag^I-catalyzed deprotection of a terminal alkyne. The methodology is highlighted by the synthesis of an amphiphilic branched [4]rotaxane. The methodology increases the ability to access ever more complicated mechanically interlocked compounds to serve in devices as sophisticated and functional molecular machinery.

Heterogeneous Catalysis through Microcontact Printing

Co-reporter:JasonM. Spruell;BonnieA. Sheriff Dr.;DorotaI. Rozkiewicz Dr.;WilliamR. Dichtel Dr.;RosemaryD. Rohde;DavidN. Reinhoudt ;J.Fraser Stoddart ;JamesR. Heath

Angewandte Chemie International Edition 2008 Volume 47( Issue 51) pp:9927-9932

Publication Date(Web):

DOI:10.1002/anie.200803480

Development of ultra-high density silicon nanowire arrays for electronics applications

Co-reporter:Dunwei Wang;Bonnie A. Sheriff;Michael McAlpine

Nano Research 2008 Volume 1( Issue 1) pp:9-21

Publication Date(Web):2008 July

DOI:10.1007/s12274-008-8005-8

This article reviews our recent progress on ultra-high density nanowires (NWs) array-based electronics. The superlattice nanowire pattern transfer (SNAP) method is utilized to produce aligned, ultra-high density Si NW arrays. We fi rst cover processing and materials issues related to achieving bulk-like conductivity characteristics from 10 20 nm wide Si NWs. We then discuss Si NW-based fi eld-effect transistors (FETs). These NWs & NW FETs provide terrifi c building blocks for various electronic circuits with applications to memory, energy conversion, fundamental physics, logic, and others. We focus our discussion on complementary symmetry NW logic circuitry, since that provides the most demanding metrics for guiding nanofabrication. Issues such as controlling the density and spatial distribution of both p-and n-type dopants within NW arrays are discussed, as are general methods for achieving Ohmic contacts to both p-and n-type NWs. These various materials and nanofabrication advances are brought together to demonstrate energy effi cient, complementary symmetry NW logic circuits.

A 160-kilobit molecular electronic memory patterned at 1011 bits per square centimetre

Co-reporter:Jonathan E. Green, Jang Wook Choi, Akram Boukai, Yuri Bunimovich, Ezekiel Johnston-Halperin, Erica DeIonno, Yi Luo, Bonnie A. Sheriff, Ke Xu, Young Shik Shin, Hsian-Rong Tseng, J. Fraser Stoddart & James R. Heath

Nature 2007 445(7126) pp:414

Publication Date(Web):2007-01-25

DOI:10.1038/nature05462

The primary metric for gauging progress in the various semiconductor integrated circuit technologies is the spacing, or pitch, between the most closely spaced wires within a dynamic random access memory (DRAM) circuit1. Modern DRAM circuits have 140 nm pitch wires and a memory cell size of 0.0408 μm2. Improving integrated circuit technology will require that these dimensions decrease over time. However, at present a large fraction of the patterning and materials requirements that we expect to need for the construction of new integrated circuit technologies in 2013 have ‘no known solution’1. Promising ingredients for advances in integrated circuit technology are nanowires2, molecular electronics3 and defect-tolerant architectures4, as demonstrated by reports of single devices5, 6, 7 and small circuits8, 9. Methods of extending these approaches to large-scale, high-density circuitry are largely undeveloped. Here we describe a 160,000-bit molecular electronic memory circuit, fabricated at a density of 1011 bits cm-2 (pitch 33 nm; memory cell size 0.0011 μm2), that is, roughly analogous to the dimensions of a DRAM circuit1 projected to be available by 2020. A monolayer of bistable, [2]rotaxane molecules10 served as the data storage elements. Although the circuit has large numbers of defects, those defects could be readily identified through electronic testing and isolated using software coding. The working bits were then configured to form a fully functional random access memory circuit for storing and retrieving information.

Modular Synthesis and Dynamics of a Variety of Donor–Acceptor Interlocked Compounds Prepared by Click Chemistry

Co-reporter:Adam B. Braunschweig Dr.;William R. Dichtel Dr.;Mark A. Olson;Ognjen Š. Miljanić Dr.;Jason M. Spruell;James R. Heath Dr.;Saeed I. Khan Dr.;J. Fraser Stoddart Dr.

Chemistry – An Asian Journal 2007 Volume 2(Issue 5) pp:634-647

Publication Date(Web):27 APR 2007

DOI:10.1002/asia.200700035

A series of donor–acceptor [2]-, [3]-, and [4]rotaxanes and self-complexes ([1]rotaxanes) have been synthesized by a threading-followed-by-stoppering approach, in which the precursor pseudorotaxanes are fixed by using Cu^I-catalyzed Huisgen 1,3-dipolar cycloaddition to attach the required stoppers. This alternative approach to forming rotaxanes of the donor–acceptor type, in which the donor is a 1,5-dioxynaphthalene unit and the acceptor is the tetracationic cyclophane cyclobis(paraquat-p-phenylene), proceeds with enhanced yields relative to the tried and tested synthetic strategies, which involve the clipping of the cyclophane around a preformed dumbbell containing π-electron-donating recognition sites. The new synthetic approach is amenable to application to highly convergent sequences. To extend the scope of this reaction, we constructed [2]rotaxanes in which one of the phenylene rings of the tetracationic cyclophane is perfluorinated, a feature which significantly weakens its association with π-electron-rich guests. The activation barrier for the shuttling of the cyclophane over a spacer containing two triazole rings was determined to be (15.5±0.1) kcal mol⁻¹ for a degenerate two-station [2]rotaxane, a value similar to that previously measured for analogous degenerate compounds containing aromatic or ethylene glycol spacers. The triazole rings do not seem to perturb the shuttling process significantly; this property bodes well for their future incorporation into bistable molecular switches.

Size-Dependent Transport and Thermoelectric Properties of Individual Polycrystalline Bismuth Nanowires

Co-reporter:A. Boukai;K. Xu;J. R. Heath

Advanced Materials 2006 Volume 18(Issue 7) pp:864-869

Publication Date(Web):24 MAR 2006

DOI:10.1002/adma.200502194

Nanofabrication methods and a device architecture are combined to allow for four-point electric, thermoelectric, and electric field-effect measurements on individual Bi nanowires. The figure shows a false-color SEM image of a typical device used in this study, with the 11 Bi nanowires shown as a red white gradient. The temperature dependence of the various transport properties as a function of nanowire width is investigated and discussed.

Cover Picture: Ground-State Equilibrium Thermodynamics and Switching Kinetics of Bistable [2]Rotaxanes Switched in Solution, Polymer Gels, and Molecular Electronic Devices (Chem. Eur. J. 1/2006)

Co-reporter:Jang Wook Choi;Amar H. Flood Dr.;David W. Steuerman Dr.;Sune Nygaard;Adam B. Braunschweig;Nicolle N. P. Moonen Dr.;Bo W. Laursen Dr.;Yi Luo Dr.;Erica DeIonno;Andrea J. Peters Dr.;Jan O. Jeppesen ;Ke Xu;J. Fraser Stoddart

Chemistry - A European Journal 2006 Volume 12(Issue 1) pp:

Publication Date(Web):9 DEC 2005

DOI:10.1002/chem.200690000

Ground-State Equilibrium Thermodynamics and Switching Kinetics of Bistable [2]Rotaxanes Switched in Solution, Polymer Gels, and Molecular Electronic Devices

Chemistry - A European Journal 2006 Volume 12(Issue 1) pp:

Publication Date(Web):1 DEC 2005

DOI:10.1002/chem.200500934

We report on the kinetics and ground-state thermodynamics associated with electrochemically driven molecular mechanical switching of three bistable [2]rotaxanes in acetonitrile solution, polymer electrolyte gels, and molecular-switch tunnel junctions (MSTJs). For all rotaxanes a π-electron-deficient cyclobis(paraquat-p-phenylene) (CBPQT⁴⁺) ring component encircles one of two recognition sites within a dumbbell component. Two rotaxanes (RATTF⁴⁺ and RTTF⁴⁺) contain tetrathiafulvalene (TTF) and 1,5-dioxynaphthalene (DNP) recognition units, but different hydrophilic stoppers. For these rotaxanes, the CBPQT⁴⁺ ring encircles predominantly (>90 %) the TTF unit at equilibrium, and this equilibrium is relatively temperature independent. In the third rotaxane (RBPTTF⁴⁺), the TTF unit is replaced by a π-extended analogue (a bispyrrolotetrathiafulvalene (BPTTF) unit), and the CBPQT⁴⁺ ring encircles almost equally both recognition sites at equilibrium. This equilibrium exhibits strong temperature dependence. These thermodynamic differences were rationalized by reference to binding constants obtained by isothermal titration calorimetry for the complexation of model guests by the CBPQT⁴⁺ host in acetonitrile. For all bistable rotaxanes, oxidation of the TTF (BPTTF) unit is accompanied by movement of the CBPQT⁴⁺ ring to the DNP site. Reduction back to TTF⁰ (BPTTF⁰) is followed by relaxation to the equilibrium distribution of translational isomers. The relaxation kinetics are strongly environmentally dependent, yet consistent with a single electromechanical-switching mechanism in acetonitrile, polymer electrolyte gels, and MSTJs. The ground-state equilibrium properties of all three bistable [2]rotaxanes were reflective of molecular structure in all environments. These results provide direct evidence for the control by molecular structure of the electronic properties exhibited by the MSTJs.

Bridging Dimensions: Demultiplexing Ultrahigh-Density Nanowire Circuits

Co-reporter:Robert Beckman;Ezekiel Johnston-Halperin;Yi Luo;Jonathan E. Green

Science 2005 Vol 310(5747) pp:465-468

Publication Date(Web):21 Oct 2005

DOI:10.1126/science.1114757

Abstract

A demultiplexer is an electronic circuit designed to separate two or more combined signals. We report on a demultiplexer architecture for bridging from the submicrometer dimensions of lithographic patterning to the nanometer-scale dimensions that can be achieved through nanofabrication methods for the selective addressing of ultrahigh-density nanowire circuits. Order log₂(N) large wires are required to address N nanowires, and the demultiplexer architecture is tolerant of low-precision manufacturing. This concept is experimentally demonstrated on submicrometer wires and on an array of 150 silicon nanowires patterned at nanowire widths of 13 nanometers and a pitch of 34 nanometers.

Cover Picture: The First Studies of a Tetrathiafulvalene-σ-Acceptor Molecular Rectifier (Chem. Eur. J. 10/2005)

Co-reporter:Gregory Ho ;Mykola Kondratenko;Dmitrii F. Perepichka ;Karin Arseneault;Michel Pézolet ;Martin R. Bryce

Chemistry - A European Journal 2005 Volume 11(Issue 10) pp:

Publication Date(Web):28 APR 2005

DOI:10.1002/chem.200590030

The First Studies of a Tetrathiafulvalene-σ-Acceptor Molecular Rectifier

Co-reporter:Gregory Ho ;Mykola Kondratenko;Dmitrii F. Perepichka ;Karin Arseneault;Michel Pézolet ;Martin R. Bryce

Chemistry - A European Journal 2005 Volume 11(Issue 10) pp:

Publication Date(Web):18 FEB 2005

DOI:10.1002/chem.200401121

Langmuir–Blodgett monolayers of a donor–acceptor diad TTF-σ-(trinitrofluorene) (8) with an extremely low HOMO–LUMO gap (0.3 eV) have been used to create molecular junction devices that show rectification behavior. By virtue of structural similarities and position of molecular orbitals, 8 is the closest well-studied analogue of the model Aviram–Ratner unimolecular rectifier (TTF-σ-TCNQ). Compressing the monolayer results in aligning the molecules, and is followed by a drastic increase in the rectification ratio. The direction of rectification depends on the electrodes used and is different in n-Si/8/Ti and Au/8/C₁₆H₃₃S-Hg junctions. The molecular nature of such behavior was corroborated by control experiments with fatty acids and by reversing the rectification direction with changing the molecular orientation (Au/D-σ-A versus Au/A-σ-D).

The Role of Physical Environment on Molecular Electromechanical Switching

Co-reporter:Amar H. Flood Dr.;Andrea J. Peters Dr.;Scott A. Vignon;David W. Steuerman Dr.;Hsian-Rong Tseng Dr.;Seogshin Kang ;J. Fraser Stoddart

Chemistry - A European Journal 2004 Volume 10(Issue 24) pp:

Publication Date(Web):24 NOV 2004

DOI:10.1002/chem.200401052

The influences of different physical environments on the thermodynamics associated with one key step in the switching mechanism for a pair of bistable catenanes and a pair of bistable rotaxanes have been investigated systematically. The two bistable catenanes are comprised of a cyclobis(paraquat-p-phenylene) (CBPQT⁴⁺) ring, or its diazapyrenium-containing analogue, that are interlocked with a macrocyclic polyether component that incorporates the strong tetrathiafulvalene (TTF) donor unit and the weaker 1,5-dioxynaphthalene (DNP) donor unit. The two bistable rotaxanes are comprised of a CBPQT⁴⁺ ring, interlocked with a dumbbell component in which one incorporates TTF and DNP units, whereas the other incorporates a monopyrrolotetrathiafulvalene (MPTTF) donor and a DNP unit. Two consecutive cycles of a variable scan rate cyclic voltammogram (10–1500 mV s⁻¹) performed on all of the bistable switches (∼1 mM) in MeCN electrolyte solutions (0.1 M tetrabutylammonium hexafluorophosphate) across a range of temperatures (258–303 K) were recorded in a temperature-controlled electrochemical cell. The second cycle showed different intensities of the two features that were observed in the first cycle when the cyclic voltammetry was recorded at fast scan rates and low temperatures. The first oxidation peak increases in intensity, concomitant with a decrease in the intensity of the second oxidation peak. This variation changed systematically with scan rate and temperature and has been assigned to the molecular mechanical movements within the catenanes and rotaxanes of the CBPQT⁴⁺ ring from the DNP to the TTF unit. The intensities of each peak were assigned to the populations of each co-conformation, and the scan-rate variation of each population was analyzed to obtain kinetic and thermodynamic data for the movement of the CBPQT⁴⁺ ring. The Gibbs free energy of activation at 298 K for the thermally activated movement was calculated to be 16.2 kcal mol⁻¹ for the rotaxane, and 16.7 and 19.2 kcal mol⁻¹ for the bipyridinium- and diazapyrenium-based bistable catenanes, respectively. These values differ from those obtained for the shuttling and circumrotational motions of degenerate rotaxanes and catenanes, respectively, indicating that the detailed chemical structure influences the rates of movement. In all cases, when the same bistable compounds were characterized in an electrolyte gel, the molecular mechanical motion slowed down significantly, concomitant with an increase in the activation barriers by more than 2 kcal mol⁻¹. Irrespective of the environment—solution, self-assembled monolayer or solid-state polymer gel—and of the molecular structure—rotaxane or catenane—a single and generic switching mechanism is observed for all bistable molecules.

Molecular-Mechanical Switch-Based Solid-State Electrochromic Devices

Co-reporter:David W. Steuerman Dr.;Hsian-Rong Tseng Dr.;Andrea J. Peters Dr.;Amar H. Flood Dr.;Jan O. Jeppesen Dr.;Kent A. Nielsen;J. Fraser Stoddart

Angewandte Chemie 2004 Volume 116(Issue 47) pp:

Publication Date(Web):24 NOV 2004

DOI:10.1002/ange.200461723

Mit bloßem Auge lässt sich die Farbänderung erkennen, die in einer Polymermatrix auftritt, wenn das gezeigte bistabile Rotaxan zwischen den für den Grundzustand (grün) und den metastabilen Zustand (rot) stehenden Cokonformeren wechselt. Damit ist nicht nur eine elektrochrome Baueinheit in Reichweite, sondern es scheint sogar ein universeller Schaltmechanismus im Bereich des Möglichen.

Molecular-Mechanical Switch-Based Solid-State Electrochromic Devices

Co-reporter:David W. Steuerman Dr.;Hsian-Rong Tseng Dr.;Andrea J. Peters Dr.;Amar H. Flood Dr.;Jan O. Jeppesen Dr.;Kent A. Nielsen;J. Fraser Stoddart

Angewandte Chemie International Edition 2004 Volume 43(Issue 47) pp:

Publication Date(Web):24 NOV 2004

DOI:10.1002/anie.200461723

You only need eyes to appreciate the color change that occurs in a polymer matrix when the bistable rotaxane shown is switched between its ground-state (green) and metastable-state (red) co-conformers. Not only is an electrochromic device within reach, but a universal switching mechanism seems to be on the cards.

Silicon chip-based patch-clamp electrodes integrated with PDMS microfluidics

Co-reporter:Rigo Pantoja, John M. Nagarah, Dorine M. Starace, Nicholas A. Melosh, Rikard Blunck, Francisco Bezanilla, James R. Heath

Biosensors and Bioelectronics 2004 Volume 20(Issue 3) pp:509-517

Publication Date(Web):15 October 2004

DOI:10.1016/j.bios.2004.02.020

We report on a silicon wafer-based device that can be used for recording macroscopic ion channel protein activities across a diverse group of cell-types. Gigaohm seals were achieved for CHO-K1 and RIN m5F cells, and both cell-attached and whole-cell mode configurations were also demonstrated. Two distinct intrinsic potassium ion channels were recorded in whole-cell mode for HIT-T15 and RAW 264.7 cells. Polydimethylsiloxane (PDMS) microfluidics were also coupled with the micromachined silicon chips in order to demonstrate that a single cell could be selectively directed to a micropore, and membrane protein currents could subsequently be recorded. These silicon chip-based devices have significant advantages over traditional micropipette approaches, and may serve as combinatorial tools for investigating membrane biophysics, pharmaceutical screening, and other bio-sensing tasks.

The Molecule–Electrode Interface in Single-Molecule Transistors

Co-reporter:Hongbin Yu Dr.;Yi Luo Dr.;Kristen Beverly;J. Fraser Stoddart ;Hsian-Rong Tseng Dr.

Angewandte Chemie International Edition 2003 Volume 42(Issue 46) pp:

Publication Date(Web):25 NOV 2003

DOI:10.1002/anie.200352352

What's in the middle matters little! Differential conductance measurements made on single-molecule rotaxanes and their precursor dumbbells in transistors with platinum electrodes reflect the molecule–electrode contacts rather than the middle section of the molecules (see diagram; the color reflects the conductance, with dark corresponding to zero current). Interface states dominate electron transport. Molecular signatures are masked and even constitutional asymmetry in the molecule is difficult to detect.

The Molecule–Electrode Interface in Single-Molecule Transistors

Co-reporter:Hongbin Yu Dr.;Yi Luo Dr.;Kristen Beverly;J. Fraser Stoddart ;Hsian-Rong Tseng Dr.

Angewandte Chemie 2003 Volume 115(Issue 46) pp:

Publication Date(Web):25 NOV 2003

DOI:10.1002/ange.200352352

Zentral und doch nicht von Bedeutung: Messungen der differentiellen Leitfähigkeit von Rotaxanmolekülen und ihren Hantel-Vorstufen in Transistoren auf Platinelektroden zeigen, dass es nicht auf den verbrückenden Mittelteil der Moleküle, sondern auf die Kontaktstellen Molekül–Elektrode ankommt (siehe Diagramm: je dunkler der Farbton, desto geringer der Strom). Der Zustand der Grenzflächen bestimmt den Elektronentransport.

Protein Signaling Networks from Single Cell Fluctuations and Information Theory Profiling

Co-reporter:Young Shik Shin, F. Remacle, Rong Fan, Kiwook Hwang, Wei Wei, Habib Ahmad, R.D. Levine, James R. Heath

Biophysical Journal (18 May 2011) Volume 100(Issue 10) pp:

Publication Date(Web):18 May 2011

DOI:10.1016/j.bpj.2011.04.025

Protein signaling networks among cells play critical roles in a host of pathophysiological processes, from inflammation to tumorigenesis. We report on an approach that integrates microfluidic cell handling, in situ protein secretion profiling, and information theory to determine an extracellular protein-signaling network and the role of perturbations. We assayed 12 proteins secreted from human macrophages that were subjected to lipopolysaccharide challenge, which emulates the macrophage-based innate immune responses against Gram-negative bacteria. We characterize the fluctuations in protein secretion of single cells, and of small cell colonies (n = 2, 3,···), as a function of colony size. Measuring the fluctuations permits a validation of the conditions required for the application of a quantitative version of the Le Chatelier's principle, as derived using information theory. This principle provides a quantitative prediction of the role of perturbations and allows a characterization of a protein-protein interaction network.

Long, Highly-Ordered High-Temperature Superconductor Nanowire Arrays

Co-reporter:Ke Xu

Nano Letter () pp:

Publication Date(Web):October 28, 2008

DOI:10.1021/nl802264x

The preparation and electrical properties of high-temperature superconductor nanowire arrays are reported for the first time. YBa2Cu3O7−δ nanowires with widths as small as 10 nm (much smaller than the magnetic penetration depth) and lengths up to 200 μm are studied by four-point electrical measurements. All nanowires exhibit a superconducting transition above liquid nitrogen temperature and a transition temperature width that depends strongly upon the nanowire dimensions. Nanowire size effects are systematically studied, and the results are modeled satisfactorily using phase-slip theories that generate reasonable parameters. These nanowires can function as superconducting nanoelectronic components over much wider temperature ranges as compared to conventional superconductor nanowires.

Fast Nonlinear Ion Transport via Field-Induced Hydrodynamic Slip in Sub-20-nm Hydrophilic Nanofluidic Transistors

Co-reporter:Udi Vermesh ; Jang Wook Choi ; Ophir Vermesh ; Rong Fan ; John Nagarah

Nano Letter () pp:

Publication Date(Web):March 5, 2009

DOI:10.1021/nl802931r

Electrolyte transport through an array of 20 nm wide, 20 μm long SiO2 nanofluidic transistors is described. At sufficiently low ionic strength, the Debye screening length exceeds the channel width, and ion transport is limited by the negatively charged channel surfaces. At source−drain biases >5 V, the current exhibits a sharp, nonlinear increase, with a 20−50-fold conductance enhancement. This behavior is attributed to a breakdown of the zero-slip condition. Implications for energy conversion devices are discussed.