You missed us!
Here are some abstracts of talks that we have given.

Nanoscience Approaches to Heterogeneity in Biological Systems
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095, USA

Cooperative Function in Atomically Precise Nanoscale Assemblies
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095, USA

Precise Chemical, Physical, and Electronic Nanoscale Contacts
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

The chemical, physical, and electronic connections that materials make to one another and to the outside world are critical. Just as the properties and applications of conventional semiconductor devices depend on these contacts, so do nanomaterials, many nanoscale measurements, and devices of the future. We discuss the important role that chemistry can play in making and optimizing precise contacts that preserve key transport and other properties. Initial nanoscale connections and measurements guide the path to future opportunities and challenges ahead. Band alignment and minimally disruptive connections are both targets and can be characterized in both experiment and theory.

Precise Chemical, Physical, and Electronic Nanoscale Contacts
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

The chemical, physical, and electronic connections that materials make to one another and to the outside world are critical. Just as the properties and applications of conventional semiconductor devices depend on these contacts, so do nanomaterials, many nanoscale measurements, and devices of the future. We discuss the important role that chemistry can play in making and optimizing precise contacts that preserve key transport and other properties. Initial nanoscale connections and measurements guide the path to future opportunities and challenges ahead. Band alignment and minimally disruptive connections are both targets and can be characterized in both experiment and theory.

Thesis Defense: Alignment Effects in Molecular Assemblies
Jeffrey J. Schwartz, Department of Physics and California NanoSystems Institute, UCLA, Los Angeles, CA 90095, USA

Departmental Student Seminar: From Poison to Small-Molecule Probe: Cyanide Self-Assembly for the Development of Room-Temperature Single-Molecule Spectroscopy
Andrew Guttentag, Department of Chemistry and California NanoSystems Institute, UCLA, Los Angeles, CA 90095, USA

Editors' Discussion: Publishing in High-Impact Journals
Paul S. Weiss, ACS Nano, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095, USA
Ali Khandemhossieni, ACS Nano, Wyss Institute, Harvard University, Cambridge, MA, USA
Luis Liz-Marzan, Langmuir, San Sebastian, Spain
Wolfgang Parak, ACS Nano, University of Marburg, Marburg, Spain

Cooperative Function in Atomically Precise Nanoscale Assemblies
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095, USA

Elucidating the Mechanism behind Spin-Dependent Charge Transport through DNA Monolayers
John M. Abendroth and Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry and Biochemistry and Materials Science and Engineering, UCLA, Los Angeles, CA 90095, USA

The possibility of selectively filtering electrons with a particular spin by chiral molecules at metal-molecule interfaces without the use of a permanent magnet has stimulated renewed interest in probing spin-dependent phenomena in adsorbed chiral molecules and assemblies. In particular, unprecedented spin selective electron transmission at room temperature has been observed through self assembled monolayers of double-stranded DNA. These surprising results demonstrate the unique and exciting potential to utilize a more versatile class of materials to combine the fields of spintronics, bioelectronics, and biomagnetics. However, the mechanism governing electron spin filtering by DNA remains elusive. Thus, we combine advanced surface chemistry with novel electrochemical characterization strategies to deconvolute the relative contributions of molecular, surface, and interface properties to spin-selective electron conduction through DNA monolayers adsorbed on ferromagnetic substrates. We probe molecular structure and substrate parameters that have been theoretically predicted to influence spin polarization such as molecular length and substrate spin-orbit coupling. Understanding the mechanism responsible for this spin-dependent effect is critical to assess the viability of implementing DNA assemblies as sources of polarized electrons in organic spintronics devices, and advancing the frontiers of room temperature spin-dependent transport.

Precise Chemical, Physical, and Electronic Nanoscale Contacts
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095, USA

The chemical, physical, and electronic connections that materials make to one another and to the outside world are critical. Just as the properties and applications of conventional semiconductor devices depend on these contacts, so do nanomaterials, many nanoscale measurements, and devices of the future. We discuss the important role that chemistry can play in making and optimizing precise contacts that preserve key transport and other properties. Initial nanoscale connections and measurements guide the path to future opportunities and challenges ahead. Band alignment and minimally disruptive connections are both targets and can be characterized in both experiment and theory.

New Approaches to Multimodal Nanoscale Imaging and Analyses
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095, USA

As most nanoscale imaging data are oversampled, significant opportunities exist in leveraging concepts, methods, and algorithms from compressive sensing and sparsity in recording data and assembling information efficiently. Orders of magnitude expansions of dynamic range and accelerations of analyses are possible. We discuss early examples of successes in this area and point to how, with sufficiently fast algorithms, image acquisition and information assembly and convergence in nanoscience, microscopy, astronomy, reconnaissance, medicine, neuroscience, and entertainment could all be improved significantly. Nanoscale imaging tools, specifically scanning probe microscopies and spectroscopic imaging methods, are excellent testbeds for these studies both because of the programmability of acquisition and because of the relatively slow typical data acquisition rates.

Elucidating the Mechanism behind Spin-Dependent Charge Transport through DNA Monolayers
John M. Abendroth and Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry and Biochemistry and Materials Science and Engineering, UCLA, Los Angeles, CA 90095, USA

The possibility of selectively filtering electrons with a particular spin by chiral molecules at metal-molecule interfaces without the use of a permanent magnet has stimulated renewed interest in probing spin-dependent phenomena in adsorbed chiral molecules and assemblies. In particular, unprecedented spin selective electron transmission at room temperature has been observed through self assembled monolayers of double-stranded DNA. These surprising results demonstrate the unique and exciting potential to utilize a more versatile class of materials to combine the fields of spintronics, bioelectronics, and biomagnetics. However, the mechanism governing electron spin filtering by DNA remains elusive. Thus, we combine advanced surface chemistry with novel electrochemical characterization strategies to deconvolute the relative contributions of molecular, surface, and interface properties to spin-selective electron conduction through DNA monolayers adsorbed on ferromagnetic substrates. We probe molecular structure and substrate parameters that have been theoretically predicted to influence spin polarization such as molecular length and substrate spin-orbit coupling. Understanding the mechanism responsible for this spin-dependent effect is critical to assess the viability of implementing DNA assemblies as sources of polarized electrons in organic spintronics devices, and advancing the frontiers of room temperature spin-dependent transport.

Multiplexed Neurochips as Screening Platforms for Neurotransmitter-Specific High-Affinity Aptamers
Nako Nakatsuka, California NanoSystems Institute and Department of Chemistry & Biochemistry, UCLA, Los Angeles, CA 90095, USA

Investigating integrated central nervous system neural circuitry at time scales pertinent to information encoding necessitates chemically specific in vivo neurotransmitter sensors that approach the size of nanometer-sized synapses and respond in milliseconds or less. To tackle this challenge, we employ aptamers as artificial receptors, which have emerged as superior synthetic alternatives to antibodies for molecular recognition. However, to realize their full potential for neurotransmitter biosensing, novel nanotools need to be developed that enable substrate-based high affinity interactions between tethered neurotransmitters and nucleic acid libraries. We have developed "neurochips" by designing and combining advanced surface chemistries, patterning methods, and high-throughput microfluidics, which can be used to screen for neurotransmitter-specific aptamers in an environment optimized for biorecognition. We have tethered dopamine molecules and employed a previously identified dopamine-specific aptamer as a test to show that our devices are functional. Furthermore, using pre-functionalized neurotransmitter-tethered molecules, we fabricated multiplexed substrates having the capacity to capture and to sort different neurotransmitter-specific aptamers while simultaneously measuring in situ binding affinities. This platform to identify aptamers targeting neurotransmitters will not only enable significant steps toward understanding chemical neurotransmission but will serve to identify other biomolecules important in brain disorders and their treatment.

Elucidating the Mechanism behind Spin-Dependent Charge Transport through DNA Monolayers
John M. Abendroth and Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry and Biochemistry and Materials Science and Engineering, UCLA, Los Angeles, CA 90095, USA

The possibility of selectively filtering electrons with a particular spin by chiral molecules at metal-molecule interfaces without the use of a permanent magnet has stimulated renewed interest in probing spin-dependent phenomena in adsorbed chiral molecules and assemblies. In particular, unprecedented spin selective electron transmission at room temperature has been observed through self assembled monolayers of double-stranded DNA. These surprising results demonstrate the unique and exciting potential to utilize a more versatile class of materials to combine the fields of spintronics, bioelectronics, and biomagnetics. However, the mechanism governing electron spin filtering by DNA remains elusive. Thus, we combine advanced surface chemistry with novel electrochemical characterization strategies to deconvolute the relative contributions of molecular, surface, and interface properties to spin-selective electron conduction through DNA monolayers adsorbed on ferromagnetic substrates. We probe molecular structure and substrate parameters that have been theoretically predicted to influence spin polarization such as molecular length and substrate spin-orbit coupling. Understanding the mechanism responsible for this spin-dependent effect is critical to assess the viability of implementing DNA assemblies as sources of polarized electrons in organic spintronics devices, and advancing the frontiers of room temperature spin-dependent transport.

Wednesday 16 March 2016, 11³⁰ AM
American Chemical Society Meeting, Spring 2016, Surface Characterization & Manipulation for Electronic Applications Symposium, Sunday 13 - Thursday 17 March 2016, San Diego, CA

¹California NanoSystems Institute and Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, California 90095, United States
²Applied Physical Chemistry, Heidelberg University, Im Neuenheimer Feld 253, 69120 Heidelberg, Germany
³Department of Material Science and Engineering, University of California, Los Angeles, Los Angeles, California 90095, United States
⁴Department of Chemistry, Pennsylvania State University, University Park, Pennsylvania 16802, United States

A vibronic resonance between Au{111} surface states and adsorbed CN vibrations has been predicted, which we target for study. We have formed stable monolayers of cyanide on Au{111} and observe a hexagonal close-packed lattice with a nearest neighbor distance of 3.8±0.5 Å. Cyanide orients normal to the surface attached via a Au-C bond. We show that the substrate-molecule coupling is particularly strong, leading to fast electron transfer from the cyanide molecules to the Au{111} substrate as measured by resonant Auger spectroscopy using the core hole clock method. The CN/Au{111} system is a simple example of a strongly interacting adsorbate-substrate system and will be the subject of a number of further studies to be discussed.

Nanoscience Approaches to Heterogeneity in Biological Systems
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095, USA

The great promise of single-molecule/assembly measurements is to understand how critical variations in structure, conformation, and environment relate to and control function. New approaches to imaging and analysis are keys to elucidating these associations. I will discuss current and upcoming advances and will pose the challenges that lie ahead in creating, developing, and applying new tools for biology and medicine. These advances include fusing spectroscopic imaging modalities and freeing up bandwidth in measurements to record simultaneous data streams and to expand our dynamic range. Recent advances in sparsity and compressive sensing can be applied both to new analysis methods and to directing measurements so as to assemble and to converge structural and functional information. Early examples will be discussed.

Chemical Lift-Off Lithography
Liane Slaughter, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095, USA

Cooperative Function in Atomically Precise Nanoscale Assemblies
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

We use molecular design, tailored syntheses, intermolecular interactions, and selective chemistry to explore the ultimate limits of miniaturization. We direct molecules into desired positions to create nanostructures, to connect functional molecules to the outside world, and to serve as test structures for measuring single or bundled molecules [1–3]. Interactions within and between molecules can be designed, directed, measured, understood, and exploited at unprecedented scales. Such interactions can be used to form precise molecular assemblies, nanostructures, and patterns, and to control and to stabilize function. We selectively test hypothesized mechanisms of function by varying molecular design, chemical environment, and measurement conditions to enable or to disable function and control using predictive and testable means. Critical to understanding these variations has been developing the means to make tens to hundreds of thousands of independent single-molecule/assembly measurements in order to develop sufficiently significant statistical distributions, while retaining the heterogeneity intrinsic in the measurements. We use a number of excitation mechanisms to induce changes in the molecules and assemblies, including electric field, light, electrochemical potential, ion binding, and chemistry [1-4]. We measure the electronic coupling of the contacts between the molecules and substrates by measuring the polarizabilities of the connected functional molecules [4]. We have likewise developed and applied the means to map buried chemical functionality and interactions [5,6]. The next steps are to learn to assemble and to operate molecules together, both cooperatively and hierarchically, in analogy to biological muscles. We discuss our initial efforts in this area, in which we find both interferences and cooperativity [2].

References
[1] S. A. Claridge, J. J. Schwartz, P. S. Weiss, ACS Nano, 2011, 5, 693-729.
[2] Y. B. Zheng, B. K. Pathem, J. N. Hohman, J. C. Thomas, M. H. Kim, P. S. Weiss, Adv. Matl., 2013, 25, 302-312.
[3] S. A. Claridge, W.-S. Liao, J. C. Thomas, Y. Zhao, H. Cao, S. Cheunkar, A. C. Serino, A. M. Andrews, P. S. Weiss, Chem. Soc. Rev., 2013, 42, 2725-2745.
[4] A. M. Moore, S. Yeganeh, Y. Yao, J. M. Tour, M. A. Ratner, P. S. Weiss, ACS Nano, 2010, 4, 7630-7636.
[5] P. Han, A. R. Kurland, A. N. Giordano, S. U. Nanayakkara, M. M. Blake, C. M. Pochas, P. S. Weiss, ACS Nano, 2009, 3, 3115-3121.
[6] J. C. Thomas, J. J. Schwartz, J. N. Hohman, S. A. Claridge, A. C. Serino, H. S. Auluck, G. Tran, K. F. Kelly, C. A. Mirkin, J. Gilles, S. J. Osher, P. S. Weiss, ACS Nano, 2015, 9, 4734-4742.

Exploring the Ultimate Limits of Miniaturization in Science, Engineering, and Medicine
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

The great promise of single-molecule/assembly measurements is to understand how critical variations in structure, conformation, and environment relate to and control function. New approaches to imaging and analysis are keys to elucidating these associations. I will discuss current and upcoming advances and will pose the challenges that lie ahead in creating, developing, and applying new tools for biology and medicine. These advances include fusing spectroscopic imaging modalities and freeing up bandwidth in measurements to record simultaneous data streams and to expand our dynamic range. Recent advances in sparsity and compressive sensing can be applied both to new analysis methods and to directing measurements so as to assemble and to converge structural and functional information. Early examples will be discussed.

Cooperative Function in Atomically Precise Nanoscale Assemblies
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

We use molecular design, tailored syntheses, intermolecular interactions, and selective chemistry to explore the ultimate limits of miniaturization. We direct molecules into desired positions to create nanostructures, to connect functional molecules to the outside world, and to serve as test structures for measuring single or bundled molecules [1-4]. Interactions within and between molecules can be designed, directed, measured, understood, and exploited at unprecedented scales. Such interactions can be used to form precise molecular assemblies, nanostructures, and patterns, and to control and to stabilize function. We selectively test hypothesized mechanisms of function by varying molecular design, chemical environment, and measurement conditions to enable or to disable function and control using predictive and testable means. Critical to understanding these variations has been developing the means to make tens to hundreds of thousands of independent single-molecule/assembly measurements in order to develop sufficiently significant statistical distributions, while retaining the heterogeneity intrinsic in the measurements. We use a number of excitation mechanisms to induce changes in the molecules and assemblies, including electric field, light, electrochemical potential, ion binding, and chemistry [1-5]. We measure the electronic coupling of the contacts between the molecules and substrates by measuring the polarizabilities of the connected functional molecules [5]. We have likewise developed and applied the means to map buried chemical functionality and interactions [6,7]. The next steps are to learn to assemble and to operate molecules together, both cooperatively and hierarchically, in analogy to biological muscles. We discuss our initial efforts in this area, in which we find both interferences and cooperativity [2].

References
[1] S. A. Claridge, J. J. Schwartz, P. S. Weiss, ACS Nano 2011, 5, 693-729.
[2] Y. B. Zheng, B. K. Pathem, J. N. Hohman, J. C. Thomas, M. H. Kim, P. S. Weiss, Adv. Matl. 2013, 25, 302-312.
[3] S. A. Claridge, W.-S. Liao, J. C. Thomas, Y. Zhao, H. Cao, S. Cheunkar, A. C. Serino, A. M. Andrews, P. S. Weiss, Chem. Soc. Rev. 2013, 42, 2725-2745.
[4] J. M. Abendroth, O. S. Bushuyev, P. S. Weiss, and C. J. Barrett, ACS Nano 2015, 9, 7746-7768.
[5] A. M. Moore, S. Yeganeh, Y. Yao, J. M. Tour, M. A. Ratner, P. S. Weiss, ACS Nano 2010, 4, 7630-7636.
[6] P. Han, A. R. Kurland, A. N. Giordano, S. U. Nanayakkara, M. M. Blake, C. M. Pochas, P. S. Weiss, ACS Nano 2009, 3, 3115-3121.
[7] J. C. Thomas, J. J. Schwartz, J. N. Hohman, S. A. Claridge, A. C. Serino, H. S. Auluck, G. Tran, K. F. Kelly, C. A. Mirkin, J. Gilles, S. J. Osher, P. S. Weiss, ACS Nano, 2015 9, 4734-4742.

Atomically Precise Nanoscale Contacts
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

The physical, electronic, mechanical, and chemical connections that materials make to one another and to the outside world are critical. Just as the properties and applications of conventional semiconductor devices depend on these contacts, so do nanomaterials, many nanoscale measurements, and devices of the future. We discuss the important roles that these contacts can play in preserving key transport and other properties. Initial nanoscale connections and measurements guide the path to future opportunities and challenges ahead. Band alignment and minimally disruptive connections are both targets and can be characterized in both experiment and theory. I discuss our initial forays into this area in a number of materials systems.

Electronic Structure, Assembly, and Chemistry of Precise Clusters
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

Precise clusters offer a new set of building blocks with unique properties that can be leveraged both individually and in materials in which their coupling can be controlled by choice of linker, dimensionality, and structure. Initial measurements in both of these worlds have been made. Isolated adsorbed or tethered clusters are probed with low-temperature scanning tunneling microscopy and spectroscopy. Even closely related elements behave differently on identical substrates. Surprising spectral variations are found for repeated measurements of single isolated, tethered clusters. In periodic solids, precise clusters joined by linkers can be measured experimentally and treated theoretically with excellent agreement, in part due to the relatively weak coupling of the clusters. This coupling can be controlled and exploited to produce materials with tailored properties. Some of the rules for predicting these properties are being developed through these initial studies and the limit to which they can be applied is being explored.

Cooperative Function in Atomically Precise Nanoscale Assemblies
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

We use molecular design, tailored syntheses, intermolecular interactions, and selective chemistry to explore the ultimate limits of miniaturization. We direct molecules into desired positions to create nanostructures, to connect functional molecules to the outside world, and to serve as test structures for measuring single or bundled molecules [1-4]. Interactions within and between molecules can be designed, directed, measured, understood, and exploited at unprecedented scales. Such interactions can be used to form precise molecular assemblies, nanostructures, and patterns, and to control and to stabilize function. We selectively test hypothesized mechanisms of function by varying molecular design, chemical environment, and measurement conditions to enable or to disable function and control using predictive and testable means. Critical to understanding these variations has been developing the means to make tens to hundreds of thousands of independent single-molecule/assembly measurements in order to develop sufficiently significant statistical distributions, while retaining the heterogeneity intrinsic in the measurements. We use a number of excitation mechanisms to induce changes in the molecules and assemblies, including electric field, light, electrochemical potential, ion binding, and chemistry [1-5]. We measure the electronic coupling of the contacts between the molecules and substrates by measuring the polarizabilities of the connected functional molecules [5]. We have likewise developed and applied the means to map buried chemical functionality and interactions [6,7]. The next steps are to learn to assemble and to operate molecules together, both cooperatively and hierarchically, in analogy to biological muscles. We discuss our initial efforts in this area, in which we find both interferences and cooperativity [2].

References
[1] S. A. Claridge, J. J. Schwartz, P. S. Weiss, ACS Nano, 2011, 5, 693-729.
[2] Y. B. Zheng, B. K. Pathem, J. N. Hohman, J. C. Thomas, M. H. Kim, P. S. Weiss, Adv. Matl., 2013, 25, 302-312.
[3] S. A. Claridge, W.-S. Liao, J. C. Thomas, Y. Zhao, H. Cao, S. Cheunkar, A. C. Serino, A. M. Andrews, P. S. Weiss, Chem. Soc. Rev., 2013, 42, 2725-2745.
[4] J. M. Abendroth, O. S. Bushuyev, P. S. Weiss, and C. J. Barrett, ACS Nano, 2015, 9, 7746-7768.
[5] A. M. Moore, S. Yeganeh, Y. Yao, J. M. Tour, M. A. Ratner, P. S. Weiss, ACS Nano, 2010, 4, 7630-7636.
[6] P. Han, A. R. Kurland, A. N. Giordano, S. U. Nanayakkara, M. M. Blake, C. M. Pochas, P. S. Weiss, ACS Nano, 2009, 3, 3115-3121.
[7] J. C. Thomas, J. J. Schwartz, J. N. Hohman, S. A. Claridge, A. C. Serino, H. S. Auluck, G. Tran, K. F. Kelly, C. A. Mirkin, J. Gilles, S. J. Osher, P. S. Weiss, ACS Nano, 2015, 9, 4734-4742.

Precise Chemical, Physical, and Electronic Nanoscale Contacts
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

The chemical, physical, and electronic connections that materials make to one another and to the outside world are critical. Just as the properties and applications of conventional semiconductor devices depend on these contacts, so do nanomaterials, many nanoscale measurements, and devices of the future. We discuss the important role that chemistry can play in making and optimizing precise contacts that preserve key transport and other properties. Initial nanoscale connections and measurements guide the path to future opportunities and challenges ahead. Band alignment and minimally disruptive connections are both targets and can be characterized in both experiment and theory.

What's on The Outside Counts Too: Surface-Dipole Modulated Assembly
Jeffrey Schwartz, California NanoSystems Institute and Department of Physics, UCLA, Los Angeles, CA 90095, USA

Nanoscience Approaches to Heterogeneity in Biological Systems
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095, USA

The great promise of single-molecule/assembly measurements is to understand how critical variations in structure, conformation, and environment relate to and control function.¹ New approaches to imaging and analysis are keys to elucidating these associations. I will discuss current and upcoming advances and will pose the challenges that lie ahead in creating, developing, and applying new tools for biology and medicine. These advances include fusing spectroscopic imaging modalities and freeing up bandwidth in measurements to record simultaneous data streams and to expand our dynamic range. Recent advances in sparsity and compressive sensing can be applied both to new analysis methods and to directing measurements so as to assemble and to converge structural and functional information. Early examples will be discussed.

¹Electrons, Photons, and Force: Quantitative Single-Molecule Measurements from Physics to Biology, S. A. Claridge, J. J. Schwartz, and P. S. Weiss, ACS Nano 5, 693 (2011).

Precise Chemical, Physical, and Electronic Nanoscale Contacts
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095, USA

The chemical, physical, and electronic connections that materials make to one another and to the outside world are critical. Just as the properties and applications of conventional semiconductor devices depend on these contacts, so do nanomaterials, many nanoscale measurements, and devices of the future. We discuss the important role that chemistry can play in making and optimizing precise contacts that preserve key transport and other properties. Initial nanoscale connections and measurements guide the path to future opportunities and challenges ahead. Band alignment and minimally disruptive connections are both targets and can be characterized in both experiment and theory.

Precise Chemical, Physical, and Electronic Nanoscale Contacts
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

The chemical, physical, and electronic connections that materials make to one another and to the outside world are critical. Just as the properties and applications of conventional semiconductor devices depend on these contacts, so do nanomaterials, many nanoscale measurements, and devices of the future. We discuss the important role that chemistry can play in making and optimizing precise contacts that preserve key transport and other properties. Initial nanoscale connections and measurements guide the path to future opportunities and challenges ahead. Band alignment and minimally disruptive connections are both targets and can be characterized in both experiment and theory.

Atomically Precise Nanoscale Contacts
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

The physical, electronic, mechanical, and chemical connections that materials make to one another and to the outside world are critical. Just as the properties and applications of conventional semiconductor devices depend on these contacts, so do nanomaterials, many nanoscale measurements, and devices of the future. We discuss the important roles that these contacts can play in preserving key transport and other properties. Initial nanoscale connections and measurements guide the path to future opportunities and challenges ahead. Band alignment and minimally disruptive connections are both targets and can be characterized in both experiment and theory. I discuss our initial forays into this area in a number of materials systems.

Precise Chemical, Physical, and Electronic Nanoscale Contacts
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095, USA

The chemical, physical, and electronic connections that materials make to one another and to the outside world are critical. Just as the properties and applications of conventional semiconductor devices depend on these contacts, so do nanomaterials, many nanoscale measurements, and devices of the future. We discuss the important role that chemistry can play in making and optimizing precise contacts that preserve key transport and other properties. Initial nanoscale connections and measurements guide the path to future opportunities and challenges ahead. Band alignment and minimally disruptive connections are both targets and can be characterized in both experiment and theory.

Spotlight on Nanotechnology in the Physical Sciences
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095, USA

Principles of Principals in Image Processing
Mercedes B. Cornelius, Miles A. Silverman, and Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

Single-molecule measurements of complex biological structures, such as proteins, are an attractive route for determining structures of important biomolecules that are difficult to analyze through conventional techniques. Using a custom-built alternating current scanning tunneling microscope we have imaged self-assembled peptide structures on graphite surfaces in both topography and microwave polarizability modes. Here, these images are analyzed to identify distinct characteristics, structures, and features of peptides at the single-molecule level. Utilizing mathematical techniques, such as two-dimensional variational mode decomposition, we are able to both segment images into domains of different structures and to identify unique structural motifs within those domains. We have been able to display principal characteristics of the two modes of the image via principal component analysis. We are working to distinguish between amino acid side chains based on differential polarizabilities characteristics of the images. Ultimately, by observing the structures of proteins at the single-molecule level, we gain insight into molecules that are otherwise extremely difficult to study. Understanding the structures of molecules, such as amyloids, allows us to evaluate disease-related proteins and to elucidate their roles in neurodegenerative diseases. Mathematical modeling and segmentation enables us to extract and analyze relevant data from a complicated system and to elucidate the structures of proteins self-assembled onto surfaces.

Determination of Structural Organization and Morphology of Amyloid Beta via Scanning Tunneling Microscopy
Diana Yugay, Lisa M. Kawakami, Dominic Goronzy, Jerome Gilles, Tze-Bin Song, Yang Yang, Ya-Hong Xie, and Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

Alzheimer's Disease (AD) is a chronic neurodegenerative disease that involves the aggregation of amyloid beta (AB) peptides in the brain. Transition metal ions, such as Cu(II) and Zn(II), are known to be abnormally concentrated in AB aggregates and synaptic areas of the brain in people with AD. A cure for AD has yet to be discovered due to the limited knowledge about cause and effect in the disease, which may involve the binding of transition metal ions to AB; thus, elucidating amino acid coordination at the binding site(s) is an important step in understanding the disease. Previously, we have demonstrated the ability to resolve sub-molecular structures of biological molecules and differentiate between side chains of individual amino acids and their orientations by using scanning tunneling microscopy (STM). In this study, we report structural elucidation of the N-terminus of AB (AB(1-16)) via STM and its structural progression in the presence and the absence of Cu(II) ions via circular dichroism, atomic force microscopy, surface-enhanced Raman spectroscopy, and cyclic voltammetry. Our findings indicate that upon the deposition of AB(1-16) on highly oriented pyrolytic graphite, AB(1-16) laminates into structured B-sheet domains. Most importantly, based on the analysis of the length and position of protruding features of Cu(II) ions within AB(1-16) peptides from STM images, we determine that Cu(II) ions participate in inter-sheet AB(1-16) binding by coordinating with two neighboring histidine residues, His13 and His14.

Nanoscience Approaches to Heterogeneity in Biological Systems
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

The great promise of single-molecule/assembly measurements is to understand how critical variations in structure, conformation, and environment relate to and control function.¹ New approaches to imaging and analysis are keys to elucidating these associations. I will discuss current and upcoming advances and will pose the challenges that lie ahead in creating, developing, and applying new tools for biology and medicine. These advances include fusing spectroscopic imaging modalities and freeing up bandwidth in measurements to record simultaneous data streams and to expand our dynamic range. Recent advances in sparsity and compressive sensing can be applied both to new analysis methods and to directing measurements so as to assemble and to converge structural and functional information. Early examples related to the BRAIN² and Microbiome³ Initiatives will be discussed.

¹Electrons, Photons, and Force: Quantitative Single-Molecule Measurements from Physics to Biology, S. A. Claridge, J. J. Schwartz, and P. S. Weiss, ACS Nano 5, 693 (2011).
²Nanotools for Neuroscience and Brain Activity Mapping, A. P. Alivisatos, A. M. Andrews, E. S. Boyden, M. Chun, G. M. Church, K. Deisseroth, J. P. Donoghue, S. E. Fraser, J. Lippincott-Schwartz, L. L. Looger, S. Masmanidis, P. L. McEuen, A. V. Nurmikko, H. Park, D. S. Peterka, C. Reid, M. L. Roukes, A. Scherer, T. J. Sejnowski, K. L. Shepard, D. Tsao, G. Turrigiano, P. S. Weiss, C. Xu, R. Yuste, and X. Zhuang, ACS Nano 7, 1850 (2013).
³Tools for the Microbiome: Nano and Beyond, J. S. Biteen, P. C. Blainey, M. Chun, G. M. Church, P. C. Dorrestein, S. E. Fraser, J. A. Gilbert, J. K. Jansson, R. Knight, J. F. Miller, A. Ozcan, K. A. Prather, E. G. Ruby, P. A. Silver, S. Taha, G. van den Engh, P. S. Weiss, G. C. L. Wong, A. T. Wright, and T. D. Young, ACS Nano 10, 6 (2016).

Nanoscience Approaches to Heterogeneity in Biological Systems
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

Multifaceted Nanobiomaterial Assemblies for Modeling Hematopoietic Stem Cell Niches
Steven Jonas, California NanoSystems Institute and Department of Pediatrics, UCLA, Los Angeles, CA 90095

Base Sequence and Structure Relationships in Spin Polarization by DNA
John M. Abendroth and Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

Spin-Dependent Electrochemistry of Perylenediimide Derivatives Noncovalently Assembled within DNA
John M. Abendroth and Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

Spin-Dependent Charge Transport through Chiral Molecular Monolayers
John M. Abendroth, California NanoSystems Institute and Departments of Chemistry & Biochemistry, UCLA, Los Angeles, CA 90095

Precise Chemical, Physical, and Electronic Nanoscale Contacts
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

The chemical, physical, and electronic connections that materials make to one another and to the outside world are critical. Just as the properties and applications of conventional semiconductor devices depend on these contacts, so do nanomaterials, many nanoscale measurements, and devices of the future. We discuss the important role that chemistry can play in making and optimizing precise contacts that preserve key transport and other properties. Initial nanoscale connections and measurements guide the path to future opportunities and challenges ahead. Band alignment and minimally disruptive connections are both targets and can be characterized in both experiment and theory.

A Career in Nanoscience So Far
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

DNA Aptamer Biosensors to Monitor Neurotransmitters in the Brain
Nako Nakatsuka, California NanoSystems Institute and Departments of Chemistry & Biochemistry, UCLA, Los Angeles, CA 90095

Atomically Precise Nanoscale Contacts
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

The physical, electronic, mechanical, and chemical connections that materials make to one another and to the outside world are critical. Just as the properties and applications of conventional semiconductor devices depend on these contacts, so do nanomaterials, many nanoscale measurements, and devices of the future. We discuss the important roles that these contacts can play in preserving key transport and other properties. Initial nanoscale connections and measurements guide the path to future opportunities and challenges ahead. Band alignment and minimally disruptive connections are both targets and can be characterized in both experiment and theory. I discuss our initial forays into this area in a number of materials systems.

Precise Chemical, Physical, and Electronic Nanoscale Contacts
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

Transition Metal Ion Binding in Amyloid Peptides
Diana Yugay, California NanoSystems Institute and Departments of Chemistry & Biochemistry, UCLA, Los Angeles, CA 90095

Nanoscience Approaches to Heterogeneity in Biological Systems
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095, USA

The great promise of single-molecule/assembly measurements is to understand how critical variations in structure, conformation, and environment relate to and control function. New approaches to imaging and analysis are keys to elucidating these associations. I will discuss current and upcoming advances and will pose the challenges that lie ahead in creating, developing, and applying new tools for biology and medicine. These advances include fusing spectroscopic imaging modalities and freeing up bandwidth in measurements to record simultaneous data streams and to expand our dynamic range. Recent advances in sparsity and compressive sensing can be applied both to new analysis methods and to directing measurements so as to assemble and to converge structural and functional information. Early examples will be discussed.

Precise Chemical, Physical, and Electronic Nanoscale Contacts
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095, USA

The chemical, physical, and electronic connections that materials make to one another and to the outside world are critical. Just as the properties and applications of conventional semiconductor devices depend on these contacts, so do nanomaterials, many nanoscale measurements, and devices of the future. We discuss the important role that chemistry can play in making and optimizing precise contacts that preserve key transport and other properties. Initial nanoscale connections and measurements guide the path to future opportunities and challenges ahead. Band alignment and minimally disruptive connections are both targets and can be characterized in both experiment and theory.

Self-Assembly of Carboxy-Functionalized Carboranethiols on Au{111}
Jun She, Dominic Goronzy, and Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

Atomically Precise Nanoscale Contacts
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

Atomically Precise Nanoscale Contacts
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095, USA

The physical, electronic, mechanical, and chemical connections that materials make to one another and to the outside world are critical. Just as the properties and applications of conventional semiconductor devices depend on these contacts, so do nanomaterials, many nanoscale measurements, and devices of the future. We discuss the important roles that these contacts can play in preserving key transport and other properties. Initial nanoscale connections and measurements guide the path to future opportunities and challenges ahead. Band alignment and minimally disruptive connections are both targets and can be characterized in both experiment and theory. I discuss our initial forays into this area in a number of materials systems.

Cooperative Function in Atomically Precise Nanoscale Assemblies
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095, USA

We use molecular design, tailored syntheses, intermolecular interactions, and selective chemistry to explore the ultimate limits of miniaturization. We direct molecules into desired positions to create nanostructures, to connect functional molecules to the outside world, and to serve as test structures for measuring single or bundled molecules. Interactions within and between molecules can be designed, directed, measured, understood, and exploited at unprecedented scales. Such interactions can be used to form precise molecular assemblies, nanostructures, and patterns, and to control and to stabilize function. We selectively test hypothesized mechanisms of function by varying molecular design, chemical environment, and measurement conditions to enable or to disable function and control using predictive and testable means. Critical to understanding these variations has been developing the means to make tens to hundreds of thousands of independent single-molecule/assembly measurements in order to develop sufficiently significant statistical distributions, while retaining the heterogeneity intrinsic in the measurements. We use a number of excitation mechanisms to induce changes in the molecules and assemblies, including electric field, light, electrochemical potential, ion binding, and chemistry. We measure the electronic coupling of the contacts between the molecules and substrates by measuring the polarizabilities of the connected functional molecules. We have likewise developed and applied the means to map buried chemical functionality and interactions. The next steps are to learn to assemble and to operate molecules together, both cooperatively and hierarchically, in analogy to biological muscles. We discuss our initial efforts in this area, in which we find both interferences and cooperativity.

Atomically Precise Nanoscale Contacts
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095, USA

The physical, electronic, mechanical, and chemical connections that materials make to one another and to the outside world are critical. Just as the properties and applications of conventional semiconductor devices depend on these contacts, so do nanomaterials, many nanoscale measurements, and devices of the future. We discuss the important roles that these contacts can play in preserving key transport and other properties. Initial nanoscale connections and measurements guide the path to future opportunities and challenges ahead. Band alignment and minimally disruptive connections are both targets and can be characterized in both experiment and theory. I discuss our initial forays into this area in a number of materials systems.

Nanoscience Approaches to Heterogeneity in Biological Systems
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095, USA

The great promise of single-molecule/assembly measurements is to understand how critical variations in structure, conformation, and environment relate to and control function. New approaches to imaging and analysis are keys to elucidating these associations. I will discuss current and upcoming advances and will pose the challenges that lie ahead in creating, developing, and applying new tools for biology and medicine. These advances include fusing spectroscopic imaging modalities and freeing up bandwidth in measurements to record simultaneous data streams and to expand our dynamic range. Recent advances in sparsity and compressive sensing can be applied both to new analysis methods and to directing measurements so as to assemble and to converge structural and functional information. Early examples will be discussed.

Nanoscience Approaches to Heterogeneity in Biological Systems
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095, USA

The great promise of single-molecule/assembly measurements is to understand how critical variations in structure, conformation, and environment relate to and control function [1]. New approaches to imaging and analysis are keys to elucidating these associations. I will discuss current and upcoming advances and will pose the challenges that lie ahead in creating, developing, and applying new tools for biology and medicine. These advances include fusing spectroscopic imaging modalities and freeing up bandwidth in measurements to record simultaneous data streams and to expand our dynamic range. Recent advances in sparsity and compressive sensing can be applied both to new analysis methods and to directing measurements so as to assemble and to converge structural and functional information. Early examples will be discussed [2]. Other advances from this area have led to the development multiplexed nanobiosensor arrays that technologically underpin and enable key measurements the BRAIN and microbiome initiatives [3,4].

Precise Chemical, Physical, and Electronic Nanoscale Contacts
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095, USA

The physical, electronic, mechanical, and chemical connections that materials make to one another and to the outside world are critical. Just as the properties and applications of conventional semiconductor devices depend on these contacts, so do nanomaterials, many nanoscale measurements, and devices of the future. We discuss the important roles that these contacts can play in preserving key transport and other properties. Initial nanoscale connections and measurements guide the path to future opportunities and challenges ahead. Band alignment and minimally disruptive connections are both targets and can be characterized in both experiment and theory. I discuss our initial forays into this area in a number of materials systems.

Chemistry and Function in Confined Spaces
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095, USA

We have developed insertion-directed assembly on surfaces in order to place functional molecules, switches and motors, into well-defined environments [1-3]. We design the matrices to interact with and to guide the molecules into position or through regioselective reactions [4]. We have developed simple, symmetric molecules for use as the components of the two-dimensional matrices so that both the confined spaces and intermolecular interactions are increasingly well defined. While much of our work has been done on flat surfaces where we get better than molecular resolution of the position and orientation of each molecule using scanning tunneling microscopy and spectroscopy, I will discuss how we are porting these same ideas over to curved and inaccessible surfaces [5]. I will also discuss new strategies for isolation, as well as how the structures that we assemble can be used to develop nanobiosensor arrays to measure the chemical signaling molecules of the brain and of the microbiome.

Keywords: nanoscience, self-assembly, cage molecules.

References
[1] S. A. Claridge, W.-S. Liao, J. C. Thomas, Y. Zhao, H. Cao, S. Cheunkar, A. C. Serino, A. M. Andrews, P. S. Weiss, Chemical Society Reviews, 2013, 42, 2725.
[2] B. K. Pathem, S. A. Claridge, Y. B. Zheng, P. S. Weiss, Annual Review of Physical Chemistry, 2013, 64, 605.
[3] Y. B. Zheng, B. K. Pathem, J. N. Hohman, M. H. Kim, P. S. Weiss, Advanced Materials, 2013, 25, 302.
[4] M. H. Kim, J. N. Hohman, Y. Cao, K. N. Houk, H. Ma, A. K.-Y. Jen, P. S. Weiss, Science, 2011, 331, 1312.
[5] A. Y. B. Zheng, J. L. Payton, T.-B. Song, B. K. Pathem, Y. Zhao, H. Ma, Y. Yang, L. Jensen, A. K.-Y. Jen, P. S. Weiss, J. Public, Nano Letters, 2012, 12, 5362.

Precise Chemical, Physical, and Electronic Nanoscale Contacts
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095, USA

The physical, electronic, mechanical, and chemical connections that materials make to one another and to the outside world are critical. Just as the properties and applications of conventional semiconductor devices depend on these contacts, so do nanomaterials, many nanoscale measurements, and devices of the future. We discuss the important roles that these contacts can play in preserving key transport and other properties. Initial nanoscale connections and measurements guide the path to future opportunities and challenges ahead. Band alignment and minimally disruptive connections are both targets and can be characterized in both experiment and theory. I discuss our initial forays into this area in a number of materials systems.

The Future of Nano
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095, USA

New Tools Lead to New Science: Challenges in Instrument Development
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095, USA

Precise Chemical, Physical, and Electronic Nanoscale Contacts
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095, USA

The physical, electronic, mechanical, and chemical connections that materials make to one another and to the outside world are critical. Just as the properties and applications of conventional semiconductor devices depend on these contacts, so do nanomaterials, many nanoscale measurements, and devices of the future. We discuss the important roles that these contacts can play in preserving key transport and other properties. Initial nanoscale connections and measurements guide the path to future opportunities and challenges ahead. Band alignment and minimally disruptive connections are both targets and can be characterized in both experiment and theory. I discuss our initial forays into this area in a number of materials systems.

Monitoring Spin Selectivity in DNA-Mediated Charge Transfer using Fluorescence Microscopy
Poster Award Winner!

John M. Abendroth, Nako Nakatsuka, Dokyun Kim, Eric E. Fullerton, Anne M. Andrews, and Paul S. Weiss
California NanoSystems Institute and Departments of Chemistry and Biochemistry and Materials Science and Engineering, Department of Psychiatry and Biobehavioral Health, Semel Institute for Neuroscience and Human Behavior, and Hatos Center for Neuropharmacology, UCLA
Center for Memory and Recording Research, UCSD

The possibility of selectively filtering electrons with a particular spin by chiral molecules at metal-molecule interfaces without the use of a permanent magnet has stimulated renewed interest in probing spin-dependent phenomena in adsorbed chiral molecules and assemblies.1-4 We measured the spin‑filtering efficiency of self-assembled monolayers of helical, double-stranded DNA on multilayer substrates that possess perpendicular magnetic anisotropy, enabling the injection of spin-polarized electrons into the DNA monolayers. The spin-filtering phenomenon was monitored using fluorescence microscopy and by taking advantage of the optical properties of water-soluble perylenediimide derivatives that noncovalently and precisely assemble within double-stranded DNA. Fluorescence quenching of the photoexcited dye molecules is dependent upon the efficiency of DNA-mediated charge transfer to metal surfaces, which can be modulated with an external magnetic field used to polarize the spins within the multilayer substrates. Controlling spin transport with light in this manner opens up new opportunities to design device architectures that utilize chiral organic species to generate and to manipulate spin-polarized currents.5,6 Current and future work will develop fundamental understanding of molecular parameters such as sequence and length that influence the spin-filtering effect.

Towards Nanoscale Biosensors to Map Signaling Molecules to Understand Brain Activity

Nako Nakatsuka, Kyung-Ae Yang, You Seung Rim, Xiaobin Xu, John M. Abendroth, Chuanzhen Zhao, Yang Yang, Milan Stojanovic, Paul S. Weiss, and Anne M. Andrews
California NanoSystems Institute and Departments of Chemistry and Biochemistry and Materials Science and Engineering, Department of Psychiatry and Biobehavioral Health, Semel Institute for Neuroscience and Human Behavior, and Hatos Center for Neuropharmacology, UCLA
Division of Experimental Therapeutics, Department of Medicine, and Department of Bioengineering, Columbia University

At its essence, brain function relies on complex extracellular chemistries between small molecule neurochemicals for information encoding. Investigating these interactions in real-time at the spatiotemporal level of neural circuits and across diverse signaling molecules necessitates the design, development, fabrication and validation of next generation in vivo biosensors. We couple the molecular recognition properties of rationally designed, chemically synthesized DNA sequences termed aptamers with direct signal detection via field-effect transistors. Aptamers can be optimized for a range of target concentrations, signal transduction, response speed, and in vivo stability. Dynamic changes in neurotransmitter concentrations are transduced into electrical signals by optimized binding-induced aptamer conformation changes that alter electric fields in close proximity to the sensor surfaces. We have tested the functionality of serotonin and dopamine specific aptamer field-effect transistors, which have shown high sensitivity with a limit of detection of ten femtomolar, approximately six orders of magnitude lower than the dissociation constant of the artificial recognition elements. These devices retain their functionality in full ionic strength biological fluids including undiluted artificial cerebrospinal fluid. We are now conducting measurements ex vivo in brain tissue homogenates derived from mice that lack serotonin to test device response upon controlled addition of serotonin while also assessing biofouling of devices. We envision highly multiplexed arrays of nanoscale sensors fabricated on the surfaces of implantable microprobes that will enable large-scale functional mapping of brain activity.

Nanoscience Approaches to Heterogeneity in Biological Systems
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095, USA

Nanoscience Approaches to Heterogeneity in Biological Systems
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095, USA

The great promise of single-molecule/assembly measurements is to understand how critical variations in structure, conformation, and environment relate to and control function. New approaches to imaging and analysis are keys to elucidating these associations. I will discuss current and upcoming advances and will pose the challenges that lie ahead in creating, developing, and applying new tools for biology and medicine. These advances include fusing spectroscopic imaging modalities and freeing up bandwidth in measurements to record simultaneous data streams and to expand our dynamic range. Recent advances in sparsity and compressive sensing can be applied both to new analysis methods and to directing measurements so as to assemble and to converge structural and functional information. Early examples will be discussed.

The Next Decade of Nanoscience and Nanotechnology
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095, USA

Precise Chemical, Physical, and Electronic Nanoscale Contacts
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095, USA

The physical, electronic, mechanical, and chemical connections that materials make to one another and to the outside world are critical. Just as the properties and applications of conventional semiconductor devices depend on these contacts, so do nanomaterials, many nanoscale measurements, and devices of the future. We discuss the important roles that these contacts can play in preserving key transport and other properties. Initial nanoscale connections and measurements guide the path to future opportunities and challenges ahead. Band alignment and minimally disruptive connections are both targets and can be characterized in both experiment and theory. I discuss our initial forays into this area in a number of materials systems.

Electrogenic Biofilms
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095, USA

Nanoscience Approaches to Heterogeneity in Biological Systems
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095, USA

The great promise of single-molecule/assembly measurements is to understand how critical variations in structure, conformation, and environment relate to and control function. New approaches to imaging and analysis are keys to elucidating these associations. I will discuss current and upcoming advances and will pose the challenges that lie ahead in creating, developing, and applying new tools for biology and medicine. These advances include fusing spectroscopic imaging modalities and freeing up bandwidth in measurements to record simultaneous data streams and to expand our dynamic range. Recent advances in sparsity and compressive sensing can be applied both to new analysis methods and to directing measurements so as to assemble and to converge structural and functional information. Early examples will be discussed.

Nanoscience Approaches to Heterogeneity in Biological Systems
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

The great promise of single-molecule/assembly measurements is to understand how critical variations in structure, conformation, and environment relate to and control function. New approaches to sensing, imaging, and analysis are keys to elucidating these associations. I will discuss current and upcoming advances and will pose the challenges that lie ahead in creating, developing, and applying new tools for biology and medicine. These advances include using biomolecular recognition in sensor arrays to probe dynamic chemistry in the brain and microbiome systems. It also includes fusing spectroscopic imaging modalities and freeing up bandwidth in measurements to record simultaneous data streams and to expand our dynamic range. Recent advances in sparsity and compressive sensing can be applied both to new analysis methods and to directing measurements so as to assemble and to converge structural and functional information. Early examples will be discussed.

Aptamer field-effect transistors as neurochemical sensors to monitor neurotransmitters in vivo
Nako Nakatsuka^2,3, nako.nakatsuka@gmail.com, Kyung-Ae Yang⁴, You Seung Rim^3,5, Xiaobin Xu², John Abendroth^2,3, Chuanzhen Zhao^2,3, Yang Yang⁵, Milan Stojanovic^4,6, Paul Weiss^2,3, Anne Andrews^1
1Department of Psychiatry and Biobehavioral Health and Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, California, United States;
²Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, California, United States;
³California NanoSystems Institute, Los Angeles, California, United States;
⁴Division of Experimental Therapeutics, Department of Medicine, Columbia University, New York, New York, United States;
⁵Department of Materials Science and Engineering, University of California, Los Angeles, Los Angeles, California, United States;
⁶Department of Biomedical Engineering, Columbia University, New York, New York, United States

Investigating brain chemistries in real time at the spatiotemporal level of neural circuits and across diverse signaling molecules necessitates neurochemical biosensors that approach these critical attributes. We couple the molecular recognition properties of rationally designed, chemically synthesized DNA sequences, termed aptamers, with direct signal detection via field-effect transistors. Aptamers can be designed for a range of target detection, signal transduction, response speed, and in vivo stability. Changes in neurotransmitter concentrations can be monitored via optimized binding-induced aptamer conformation changes that are transduced into electrical signals. Reversible binding of target neurotransmitters such as serotonin and dopamine by specific aptamers are hypothesized to shift electric potentials in close proximity to FET surfaces, resulting in conductance changes. Serotonin- and dopamine-specific aptamer field-effect transistors have high sensitivity with a limit of detection of 10 fM, approximately six orders of magnitude lower than the dissociation constant of the artificial recognition elements. These devices retain their functionality in full ionic strength biological fluids including artificial cerebrospinal fluid. We are now conducting measurements ex vivo in brain tissue homogenates of Tph2 knockout mice that lack serotonin to test device response upon controlled addition of serotonin while assessing biofouling of devices. We envision unprecedented capacity to measure neurochemical signaling directly, in vivo, and in real time, which will impact our understanding of brain function in relation to complex behaviors.

Proposing a two-molecule multiplexed neuromorphic system: The first step towards a chemically based artificial brain
Nako Nakatsuka^1,3, Chuanzhen Zhao^1,2, John Abendroth^1,2, Huajun Chen^2,4, Kevin Cheung^1,2, Stemer Dominik^2,4, Leonardo Scarabelli^1,2, scarabelli.leonardo@gmail.com, Kyung-Ae Yang5, Bowen Zhu^2,4, Hongyan Yang³, Yang Yang^2,4, Milan Stojanovic^5,6, Paul Weiss^1,2, Anne Andrews2,3
¹Chemistry & Biochemistry, University of California Los Angeles, Los Angeles, California, United States;
²California NanoSystems Institute, University of California Los Angeles, Los Angeles, California, United States;
³Department of Psychiatry & Behavioral Health, University of California Los Angeles, Los Angeles, California, United States;
⁴Department of Materials Science & Engineering, University of California Los Angeles, Los Angeles, California, United States;
⁵Division of Experimental Therapeutics, Department of Medicine, Columbia University, New York, New York, United States;
⁶Department of Biomedical Engineering, Columbia University, New York, New York, United States

Information acquisition, processing, and storage involving brain neurons consists of electrical and chemical components. While functionally organized micro- and nanostructures have been developed to model electrical aspects of brain neurotransmission, the complexities of chemical transmission cannot be investigated using these structures as yet. Examples of the fabrication of artificial synapses in neuromorphic systems based purely on electronic synapses exploit mechanisms such as fingering via oxide or sulfide reduction. Despite some promising results, these approaches completely overlook the highly multiplexed and heterogeneous chemical networks of neurotransmitter molecules that are fundamental to complex brain function.

We propose a synthetic multi-molecule neuromorphic system, initially employing two native neurotransmitters and related molecules. Our approach is based on state-of-the-art aptamer-based field-effect transistor sensors that have been optimized for responding to specific neurotransmitters. These sensors are placed on the same substrate and are able to work simultaneously and in an interconnected manner with one another, i.e., the concentration of one analyte influences the concentration of the other, consequently altering the responses of the corresponding sensor. This biomolecular analog-to-digital transducer represents a basic working principle behind chemical transmission and information processing in synapses, opening new avenues for the study of brain chemistry, molecular networks, and for introducing native biological strategies to enrich the potential capabilities of neuromorphic computing.

Polymer pen chemical lift-off lithography
Xiaobin Xu¹, xxu.uta@gmail.com, Qing Yang¹, Kevin Cheung¹, Chuanzhen Zhao¹, Natcha Wattanatorn¹, Jason Belling¹, John Abendroth¹, Liane Siu Slaughter¹, Chad Mirkin⁴, Anne Andrews^1,3, and Paul S. Weiss^1,2
1California NanoSystems Institute and Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, California, United States;
²Department of Materials Science and Engineering, University of California, Los Angeles, Los Angeles, California, United States;
³Department of Psychiatry and Biobehavioral Health, Semel Institute for Neuroscience and Human Behavior, and Hatos Center for Neuropharmacology, University of California, Los Angles, Los Angeles, California, United States;
⁴International Institute for Nanotechnology and Department of Chemistry and Materials Science & Engineering, Northwestern University, Evanston, Illinois, United States

We combine chemical lift-off lithography (CLL) with large arrays of polymer pens with sub-20-nm tips, developing polymer pen chemical lift-off lithography (PPCLL). We demonstrated the feasibility of PPCLL with experiments using v-shaped polymer pen arrays and associated simulations. Simulation results show a nanometer-scale quadratic relationship between the contact linewidth and two variables: base linewidth of the polymer pen and vertical compression. We invented a supporting arm system and designed a series of v-shaped polymer pens with known height differences to control precisely the relative vertical position of each polymer pens at sub-20-nm scale, which mimicked a high-precision scanning stage. In this way, we successfully obtained linear array patterns with linewidths from sub-50-nm to sub-500-nm with minimum sub-20-nm linewidth increment tunability. The CLL pattern linewidth perfectly matched the simulations. These results suggest that through the proper design of the supporting arms to suitable positions and the base linewidth of the polymer pen arrays, one can completely eliminate the need for the scanning stage system in PPCLL to increase the throughput and to reduce cost. We also showed that PPCLL can be used to design and to fabricate DNA microarrays efficiently by backfilling the patterns after PPCLL with probe DNA, and subsequently hybridizing with complementary target sequences.

New Dimensions in Patterning: Placement and Metrology of Chemical Functionality at All Scales
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

We place single molecules and assemblies into precisely controlled environments on surfaces. The inserted assemblies and the monolayer matrices that contain them can be designed so as to interact directly, to give stability or other properties to functional supramolecular assemblies. New families of highly symmetric molecules are being developed to yield even greater control and are enabling elucidation of the key design parameters of both the molecules and assemblies. These design elements, in turn, enable controlled chemical patterning from the sub-nanometer to the centimeter scales. We simultaneously develop metrology tools for these methods to give unprecedented insight on the structures, function, and properties of these assemblies.

Proposing a two-molecule multiplexed neuromorphic system: The first step towards a chemically based artificial brain
Nako Nakatsuka^1,3, Chuanzhen Zhao^1,2, John Abendroth^1,2, Huajun Chen^2,4, Kevin Cheung^1,2, Stemer Dominik^2,4, Leonardo Scarabelli^1,2, scarabelli.leonardo@gmail.com, Kyung-Ae Yang5, Bowen Zhu^2,4, Hongyan Yang³, Yang Yang^2,4, Milan Stojanovic^5,6, Paul Weiss^1,2, Anne Andrews^2,3
1Chemistry & Biochemistry, University of California Los Angeles, Los Angeles, California, United States;
²California NanoSystems Institute, University of California Los Angeles, Los Angeles, California, United States;
³Department of Psychiatry & Behavioral Health, University of California Los Angeles, Los Angeles, California, United States;
⁴Department of Materials Science & Engineering, University of California Los Angeles, Los Angeles, California, United States;
⁵Division of Experimental Therapeutics, Department of Medicine, Columbia University, New York, New York, United States;
⁶Department of Biomedical Engineering, Columbia University, New York, New York, United States

Information acquisition, processing, and storage involving brain neurons consists of electrical and chemical components. While functionally organized micro- and nanostructures have been developed to model electrical aspects of brain neurotransmission, the complexities of chemical transmission cannot be investigated using these structures as yet. Examples of the fabrication of artificial synapses in neuromorphic systems based purely on electronic synapses exploit mechanisms such as fingering via oxide or sulfide reduction. Despite some promising results, these approaches completely overlook the highly multiplexed and heterogeneous chemical networks of neurotransmitter molecules that are fundamental to complex brain function.

We propose a synthetic multi-molecule neuromorphic system, initially employing two native neurotransmitters and related molecules. Our approach is based on state-of-the-art aptamer-based field-effect transistor sensors that have been optimized for responding to specific neurotransmitters. These sensors are placed on the same substrate and are able to work simultaneously and in an interconnected manner with one another, i.e., the concentration of one analyte influences the concentration of the other, consequently altering the responses of the corresponding sensor. This biomolecular analog-to-digital transducer represents a basic working principle behind chemical transmission and information processing in synapses, opening new avenues for the study of brain chemistry, molecular networks, and for introducing native biological strategies to enrich the potential capabilities of neuromorphic computing.

Cage Molecule Self-Assembly
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

We have shown that upright, symmetric cage molecules self-assembled on surfaces have simple domain and defect structures. Unlike linear molecules, such as alkanethiols on Au{111}, these cage molecules do not tilt and do not conformationally relax. The lattices of the cage molecules are determined by the projections of the cages on the surface. Thus, different isomers, such as carboranethiols on Au{111}, form identical lattice structures. These monolayers enable key tests of simple phenomena, such as the effects of dipole moment direction and amplitude. For example, molecules with dipoles parallel to the surface form nonpolar monolayers and outcompete molecules with dipoles normal the surface, which form polar monolayers. These properties can be measured both at the macroscopic and nanoscopic scales. We understand the enhanced stability of the nonpolar surfaces to aligned dipoles in the monolayers and set out to measure such effects. Using combinations of spectroscopic imaging and novel image analyses, we find that dipoles do align, even across domain boundaries. We use mixed self-assembled monolayers of carboranes to tune and to optimize the band alignment of organic electronic devices without changing the morphology of the active layer. We also assemble multifunctionalized cage molecules and show that we can protonate and deprotonate thiol(ate)s to change the valency of attachment to the surface through simple reactions.

Spin selectivity in DNA-mediated charge transport: Base sequence and structure relationships
John Abendroth^1,2, abend@chem.ucla.edu, Nako Nakatsuka1,², Matthew Ye^1,2, Dokyun Kim⁴, Eric Fullerton⁴, Anne Andrews^1,3, Paul Weiss^1,2
1Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, California, United States;
²California NanoSystems Institute, UCLA, Los Angeles, California, United States;
³Department of Psychiatry and Biobehavioral Health, University of California, Los Angeles, Los Angeles, California, United States;
⁴Center for Memory and Recording Research, University of California, San Diego, San Diego, California, United States

Self-assembled monolayers of chiral molecules on metal and semiconducting surfaces have recently demonstrated the capability to filter transmitted electrons depending on spin orientation and the handedness of the molecules. This phenomenon, termed the chiral-induced spin selectivity effect, has renewed interest in probing spin-dependent phenomena in adsorbed chiral molecules, including self-assembled monolayers of double-stranded DNA. While the factors that affect DNA-mediated charge transfer have been extensively studied, the influence of DNA base sequence, GC content, or helical geometry on the spin selectivity in transmitted electrons has not been systematically investigated. We probed the dependence of spin polarization in DNA-mediated charge transfer on nitrogenous base sequence as a means to study spin selectivity in both coherent tunneling and incoherent hopping of charge carriers through helical molecules. Self-assembled monolayers of DNA with varying sequences were formed on multilayer substrates that possess perpendicular magnetic anisotropy, enabling the injection of spin-polarized electrons into the monolayers. The spin-filtering phenomenon was monitored using fluorescence microscopy and photoelectrochemistry by taking advantage of the optical properties of water-soluble perylenediimide derivatives that noncovalently and precisely assemble within double-stranded DNA. Competing charge-transfer pathways that lead to fluorescence or photocurrent generation following photoexcitation of the dye molecules are dependent upon the efficiency of DNA-mediated charge transfer to metal surfaces. This efficiency can be modulated with an external magnetic field used to polarize the spins within the multilayer substrates. Controlling spin transport with light in this manner opens up new opportunities to design device architectures that utilize chiral organic species to generate and to manipulate spin-polarized currents.

Cooperative Function in Atomically Precise Nanoscale Assemblies
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095, USA

We use molecular design, tailored syntheses, intermolecular interactions, and selective chemistry to explore the ultimate limits of miniaturization. We direct molecules into desired positions to create nanostructures, to connect functional molecules to the outside world, and to serve as test structures for measuring single or bundled molecules. Interactions within and between molecules can be designed, directed, measured, understood, and exploited at unprecedented scales. Such interactions can be used to form precise molecular assemblies, nanostructures, and patterns, and to control and to stabilize function. We selectively test hypothesized mechanisms of function by varying molecular design, chemical environment, and measurement conditions to enable or to disable function and control using predictive and testable means. Critical to understanding these variations has been developing the means to make tens to hundreds of thousands of independent single-molecule/assembly measurements in order to develop sufficiently significant statistical distributions, while retaining the heterogeneity intrinsic in the measurements. We use a number of excitation mechanisms to induce changes in the molecules and assemblies, including electric field, light, electrochemical potential, ion binding, and chemistry. We measure the electronic coupling of the contacts between the molecules and substrates by measuring the polarizabilities of the connected functional molecules. We have likewise developed and applied the means to map buried chemical functionality and interactions. The next steps are to learn to assemble and to operate molecules together, both cooperatively and hierarchically, in analogy to biological muscles. We discuss our initial efforts in this area, in which we find both interferences and cooperativity.

Nanoscale Optical Interactions in Precise Assemblies
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

We use molecular design, tailored syntheses, intermolecular interactions, and selective chemistry to direct molecules into desired positions to create nanostructures with controlled environments and dimensionality, to connect functional molecules to the outside world, and to serve as test structures for measuring single or bundled molecules and assemblies. We have developed and applied new multimodal nanoscale analysis tools based on the scanning tunneling microscope (STM) to measure structure, function, and spectra simultaneously. We are particularly interested in the interactions of photons with precisely assembled structures. The measured results of photoexcitation include photoconductivity and regioselective reaction. We apply this method to optimize molecules and materials for energy conversion and storage. Related imaging spectroscopies we have developed give access to the cooperative action of assembled molecular motors and the identification and orientations of parts of molecules such as amyloid-forming oligopeptides without averaging and without the need to crystallize the biomolecular assemblies. Concepts from sparsity and compressive sensing are developed and applied to guide efficient data acquisition and to accelerate data analysis and information assembly.

Precise Chemical, Physical, and Electronic Nanoscale Contacts
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

Precise Chemical, Physical, and Electronic Nanoscale Contacts
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

Nanoscience Approaches to Heterogeneity in Biological Systems
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

The great promise of single-molecule/assembly measurements is to understand how critical variations in structure, conformation, and environment relate to and control function. New approaches to sensing, imaging, and analysis are keys to elucidating these associations. I will discuss current and upcoming advances and will pose the challenges that lie ahead in creating, developing, and applying new tools for biology and medicine. These advances include using biomolecular recognition in nanobiosensor arrays to probe dynamic chemistry in the brain and microbiome systems. It also includes fusing spectroscopic imaging modalities and freeing up bandwidth in measurements to record simultaneous data streams and to expand our dynamic range. Recent advances in sparsity and compressive sensing can be applied both to new analysis methods and to directing measurements so as to assemble and to converge structural and functional information. Early examples will be discussed.

Precise Chemical, Physical, and Electronic Nanoscale Contacts
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

The great promise of single-molecule/assembly measurements is to understand how critical variations in structure, conformation, and environment relate to and control function. New approaches to sensing, imaging, and analysis are keys to elucidating these associations. I will discuss current and upcoming advances and will pose the challenges that lie ahead in creating, developing, and applying new tools for biology and medicine. These advances include using biomolecular recognition in nanobiosensor arrays to probe dynamic chemistry in the brain and microbiome systems. It also includes fusing spectroscopic imaging modalities and freeing up bandwidth in measurements to record simultaneous data streams and to expand our dynamic range. Recent advances in sparsity and compressive sensing can be applied both to new analysis methods and to directing measurements so as to assemble and to converge structural and functional information. Early examples will be discussed.

Exploring the Ultimate Limits of Miniaturization and Global Opportunities in Nanoscience and Nanotechnology
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

Two seemingly conflicting trends in nanoscience and nanotechnology are our increasing ability to reach the limits of atomically precise structures and our growing understanding of the importance of heterogeneity in the structure and function of molecules and nanoscale assemblies. I will discuss the challenges, opportunities, and consequences of pursuing strategies to address these goals. In our laboratories, we use molecular design, tailored syntheses, intermolecular interactions, and selective chemistry to explore the ultimate limits of miniaturization. We direct molecules into desired positions to create nanostructures, to connect functional molecules to the outside world, and to serve as test structures for measuring single or bundled molecules. Interactions within and between molecules can be designed, directed, measured, understood, and exploited at unprecedented scales. Such interactions can be used to form precise molecular assemblies, nanostructures, and patterns, and to control and to stabilize function. Critical to understanding these variations has been developing the means to make tens to hundreds of thousands of independent single-molecule/assembly measurements in order to develop sufficiently significant statistical distributions, while retaining the intrinsic heterogeneity in the measured function of the molecules and assemblies. We have likewise developed and applied the means to map buried chemical functionality and interactions. The next steps are to apply these ideas to biomolecular assemblies and larger biological systems to understand the variations in structure and function that have been inaccessible to study.

Cooperative Function in Atomically Precise Nanoscale Assemblies
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095, USA and Institut National de la Recherche Scientifique (INRS) Centre for Energy, Materials and Telecommunications, Montreal, Quebec, Canada

We use molecular design, tailored syntheses, intermolecular interactions, and selective chemistry to explore the ultimate limits of miniaturization. We direct molecules into desired positions to create nanostructures, to connect functional molecules to the outside world, and to serve as test structures for measuring single or bundled molecules. Interactions within and between molecules can be designed, directed, measured, understood, and exploited at unprecedented scales. Such interactions can be used to form precise molecular assemblies, nanostructures, and patterns, and to control and to stabilize function. We selectively test hypothesized mechanisms of function by varying molecular design, chemical environment, and measurement conditions to enable or to disable function and control using predictive and testable means. Critical to understanding these variations has been developing the means to make tens to hundreds of thousands of independent single-molecule/assembly measurements in order to develop sufficiently significant statistical distributions, while retaining the heterogeneity intrinsic in the measurements. We use a number of excitation mechanisms to induce changes in the molecules and assemblies, including electric field, light, electrochemical potential, ion binding, and chemistry. We measure the electronic coupling of the contacts between the molecules and substrates by measuring the polarizabilities of the connected functional molecules. We have likewise developed and applied the means to map buried chemical functionality and interactions. The next steps are to learn to assemble and to operate molecules together, both cooperatively and hierarchically, in analogy to biological muscles. We discuss our initial efforts in this area, in which we find both interferences and cooperativity.

Exploring the Ultimate Limits of Miniaturization and Global Opportunities in Nanoscience and Nanotechnology
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

Exploring the Ultimate Limits of Miniaturization
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

We use molecular design, tailored syntheses, intermolecular interactions, and selective chemistry to explore the ultimate limits of miniaturization. We direct molecules into desired positions to create nanostructures, to connect functional molecules to the outside world, and to serve as test structures for measuring single or bundled molecules. Interactions within and between molecules can be designed, directed, measured, understood, and exploited at unprecedented scales. Such interactions can be used to form precise molecular assemblies, nanostructures, and patterns, and to control and to stabilize function. We selectively test hypothesized mechanisms of function by varying molecular design, chemical environment, and measurement conditions to enable or to disable function and control using predictive and testable means. Critical to understanding these variations has been developing the means to make tens to hundreds of thousands of independent single-molecule/assembly measurements in order to develop sufficiently significant statistical distributions, while retaining the intrinsic heterogeneity in the measured function of the molecules and assemblies. We have likewise developed and applied the means to map buried chemical functionality and interactions. The next steps are to apply these ideas to biomolecular assemblies and larger biological systems to understand the variations in structure and function that have been inaccessible to study.

Aptamer-Functionalized Field-Effect Transistors for Neurotransmitter Sensing
Nako Nakatsuka, Department of Chemistry & Biochemistry, UCLA, Los Angeles, CA 90095

The BRAIN Initiative aims to unite nanotechnology and neuroscience to investigate neural circuitry within the complex landscape of the brain at the spatiotemporal scales pertinent to information encoding. Investigating how malfunctioning neural networks, which underlie brain-related disorders, are associated with neurotransmitter flux necessitates chemically specific, in vivo neurotransmitter sensors. We propose coupling the molecular recognition properties of rationally designed, chemically synthesized DNA sequences, termed aptamers, with direct electronic detection via field-effect transistors. However, the discovery of neurotransmitter-specific aptamers has been impeded by conventional in vitro screening techniques. Thus, we developed "neurochips" having precise surface chemistries that enable high-affinity interactions between aptamers and target neurotransmitter molecules. Neurochips are able to capture and to sort aptamers targeting different neurotransmitters.

In parallel, we isolated high-affinity serotonin- and dopamine-specific aptamers via an alternative screening method. We then functionalized these aptamers onto the semiconducting channels of field-effect transistor arrays to monitor changes in neurotransmitter concentrations. We hypothesized that optimized binding-induced aptamer conformation changes will be transduced into electrical signals. Serotonin- and dopamine-specific devices showed high sensitivity with a detection limit of 10 fM. These devices retain their functionality in full ionic strength biological fluids including ex vivo brain tissue, suggesting a detection mechanism that corresponds to charge motion within Debye length limitations. We envision unprecedented capacity to measure neurochemical signaling directly, in vivo¸ and in real time, which will ultimately impact our understanding of brain function in relation to complex behaviors.

Global Opportunities in Nanoscience and Nanotechnology
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

Two seemingly conflicting trends in nanoscience and nanotechnology are our increasing ability to reach the limits of atomically precise structures and our growing understanding of the importance of heterogeneity in the structure and function of molecules and nanoscale assemblies. I will discuss the challenges, opportunities, and consequences of pursuing strategies to address these goals. In our laboratories, we are taking the first steps to exploit precise assembly to optimize properties such as perfect electronic contacts in materials. We are also developing the means to make tens to hundreds of thousands of independent multimodal nanoscale measurements in order to understand the variations in structure and function that have previously been inaccessible in both synthetic and biological systems.

Much Ado about Nearly Nothing: Nanotech and the Future of Energy
Moderated by Walter Isaacson, Aspen Institute
Sanjoy Banerjee, CUNY Energy Institute
Yury Gogotsi, Drexel University
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

Nanotechnology's Promise: A Big Risk in a Small Package?
Moderated by Andrew Revkin, ProPublica.org
Vicki Colvin, Brown University
Ponisseril Somasundaran, Columbia University
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

Precise Chemical, Physical, and Electronic Nanoscale Contacts
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

CEITEC and Fulbright Scholar Lecture, Brno, Czech Republic
Precise Chemical, Physical, and Electronic Nanoscale Contacts
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

Cooperative Function in Atomically Precise Nanoscale Assemblies
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

Cooperative Function in Atomically Precise Nanoscale Assemblies
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

Precise Chemical, Physical, and Electronic Nanoscale Contacts
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

Tutorial on Patterning across Scales
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

Precise Chemical, Physical, and Electronic Nanoscale Contacts
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

Panel on Entrepreneurship
Christian Teichert, Austrian School of Mines
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095
Roland Wiesendanger, University of Hamburg, Hamburg, Germany

Fabricating Germanium Interfaces for Battery Applications
Andrew Serino, Department of Materials Science & Engineering, UCLA, Los Angeles, CA 90095

Imaging, Understanding, and Leveraging Buried Interactions in Supramolecular Assemblies
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

Structural domains is self-assembled systems are well known. The types of domain boundaries can be simplified by using symmetric building blocks. Likewise, interactions can be designed into the building blocks to add stability to the systems. By developing new imaging tools that let us visualize these interaction networks, we have discovered that buried networks can cross structural domain boundaries, regions of disorder, and substrate step edges in monolayer systems.^1-3 The interactions, their ranges and the consequences of these effects will be discussed.

1. Heads and Tails: Simultaneous Exposed and Buried Interface Imaging of Monolayers, P. Han, A. R. Kurland, A. N. Giordano, S. U. Nanayakkara, M. M. Blake, C. M. Pochas, and P. S. Weiss, ACS Nano 3, 3115 (2009).
2. Defect-Tolerant Aligned Dipoles within Two-Dimensional Plastic Lattices, J. C. Thomas, J. J. Schwartz, J. N. Hohman, S. A. Claridge, H. S. Auluck, A. C. Serino, A. M. Spokoyny, G. Tran, K. F. Kelly, C. A. Mirkin, J. Gilles, S. J. Osher, and P. S. Weiss, ACS Nano 9, 4734 (2015).
3. Mapping Buried Hydrogen-Bonding Networks, J. C. Thomas, D. P. Goronzy, K. Dragomiretskiy, D. Zosso, J. Gilles, S. J. Osher, A. L. Bertozzi, and P. S. Weiss, ACS Nano 10, 5446 (2016).

Cooperative Function in Atomically Precise Nanoscale Assemblies
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095, USA

We use molecular design, tailored syntheses, intermolecular interactions, and selective chemistry to explore the ultimate limits of miniaturization. We direct molecules into desired positions to create nanostructures, to connect functional molecules to the outside world, and to serve as test structures for measuring single or bundled molecules. Interactions within and between molecules can be designed, directed, measured, understood, and exploited at unprecedented scales. Such interactions can be used to form precise molecular assemblies, nanostructures, and patterns, and to control and to stabilize function. We selectively test hypothesized mechanisms of function by varying molecular design, chemical environment, and measurement conditions to enable or to disable function and control using predictive and testable means. Critical to understanding these variations has been developing the means to make tens to hundreds of thousands of independent single-molecule/assembly measurements in order to develop sufficiently significant statistical distributions, while retaining the heterogeneity intrinsic in the measurements. We use a number of excitation mechanisms to induce changes in the molecules and assemblies, including electric field, light, electrochemical potential, ion binding, and chemistry. We measure the electronic coupling of the contacts between the molecules and substrates by measuring the polarizabilities of the connected functional molecules. We have likewise developed and applied the means to map buried chemical functionality and interactions. The next steps are to learn to assemble and to operate molecules together, both cooperatively and hierarchically, in analogy to biological muscles. We discuss our initial efforts in this area, in which we find both interferences and cooperativity.

Global Opportunities in Nanoscience and Nanotechnology
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

Two seemingly conflicting trends in nanoscience and nanotechnology are our increasing ability to reach the limits of atomically precise structures and our growing understanding of the importance of heterogeneity in the structure and function of molecules and nanoscale assemblies. By having developed the "eyes" to see, to record spectra, and to measure function at the nanoscale, we have been able to fabricate structures with precision as well as to understand the important and intrinsic heterogeneity of function found in these assemblies.

I will discuss the challenges, opportunities, and consequences of pursuing strategies to address both precision on the one hand and heterogeneity on the other [1]. In our laboratories, we are taking the first steps to exploit precise assembly to optimize properties such as perfect electronic contacts in materials [2]. We are also developing the means to make tens to hundreds of thousands of independent multimodal nanoscale measurements in order to understand the variations in structure and function that have previously been inaccessible in both synthetic and biological systems [3,4].

Another outcome of the development of our field has been our ability to communicate across fields [5,6]. This skill that we develop in our students and colleagues has enhanced and accelerated the impact of nanoscience and nanotechnology on other fields, such as neuroscience and the microbiome [7,8]. I will discuss the opportunities presented by these entanglements and give recent examples of advances enabled by nanoscience and nanotechnology [9,10].

A Discussion on the NAKFI Process
Brandon Ballengee,
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095
Moderated by JD Talasek, Cultural Programs of the National Academy of Sciences, Washington, DC

Addressing Heterogeneity in Biological Systems
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

Precise Chemical, Physical, and Electronic Nanoscale Contacts
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

The physical, electronic, mechanical, and chemical connections that materials make to one another and to the outside world are critical. Just as the properties and applications of conventional semiconductor devices depend on these contacts, so do nanomaterials, many nanoscale measurements, and devices of the future. We discuss the important roles that these contacts can play in preserving key transport and other properties. Initial nanoscale connections and measurements guide the path to future opportunities and challenges ahead. Band alignment and minimally disruptive connections are both targets and can be characterized in both experiment and theory. I discuss our initial forays into this area in a number of materials systems.

Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

Global Opportunities in Nanoscience and Nanotechnology
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

Two seemingly conflicting trends in nanoscience and nanotechnology are our increasing ability to reach the limits of atomically precise structures and our growing understanding of the importance of heterogeneity in the structure and function of molecules and nanoscale assemblies. By having developed the "eyes" to see, to record spectra, and to measure function at the nanoscale, we have been able to fabricate structures with precision as well as to understand the important and intrinsic heterogeneity of function found in these assemblies.

I will discuss the challenges, opportunities, and consequences of pursuing strategies to address both precision on the one hand and heterogeneity on the other. In our laboratories, we are taking the first steps to exploit precise assembly to optimize properties such as perfect electronic contacts in materials. We are also developing the means to make tens to hundreds of thousands of independent multimodal nanoscale measurements in order to understand the variations in structure and function that have previously been inaccessible in both synthetic and biological systems.

Another outcome of the development of our field has been our ability to communicate across fields. This skill that we develop in our students and colleagues has enhanced and accelerated the impact of nanoscience and nanotechnology on other fields, such as neuroscience and the microbiome. I will discuss the opportunities presented by these entanglements and give recent examples of advances enabled by nanoscience and nanotechnology.

Precise Chemical, Physical, and Electronic Nanoscale Contacts
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

The physical, electronic, mechanical, and chemical connections that materials make to one another and to the outside world are critical. Just as the properties and applications of conventional semiconductor devices depend on these contacts, so do nanomaterials, many nanoscale measurements, and devices of the future. We discuss the important roles that these contacts can play in preserving key transport and other properties. Initial nanoscale connections and measurements guide the path to future opportunities and challenges ahead. Band alignment and minimally disruptive connections are both targets and can be characterized in both experiment and theory. I discuss our initial forays into this area in a number of materials systems.

The Future of Graphene
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

Nanoscale Optical Interactions in Precise Assemblies
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

We use molecular design, tailored syntheses, intermolecular interactions, and selective chemistry to direct molecules into desired positions to create nanostructures with controlled environments and dimensionality, to connect functional molecules to the outside world, and to serve as test structures for measuring single or bundled molecules and assemblies. We have developed and applied new multimodal nanoscale analysis tools based on the scanning tunneling microscope (STM) to measure structure, function, and spectra simultaneously. We are particularly interested in the interactions of photons with precisely assembled structures. The measured results of photoexcitation include photoconductivity and regioselective reaction. We apply this method to optimize molecules and materials for energy conversion and storage. Related imaging spectroscopies we have developed give access to the cooperative action of assembled molecular motors and the identification and orientations of parts of molecules such as amyloid-forming oligopeptides without averaging and without the need to crystallize the biomolecular assemblies. Concepts from sparsity and compressive sensing are developed and applied to guide efficient data acquisition and to accelerate data analysis and information assembly.

Nanobiosensor arrays for multiplexed measurements of the spatiotemporal dynamics of neurotransmitters and microbiome signalomics
Paul S. Weiss^1,2,3 and Anne M. Andrews^1,2,4
1California NanoSystems Institute and Departments of ²Chemistry & Biochemistry, ³Materials Science & Engineering, and ⁴Psychiatry, UCLA, Los Angeles, CA 90095

Investigating multiplexed biochemical signaling requires sensitive and specific detection at the time and length scales of function. We couple the molecular recognition properties of rationally designed, chemically synthesized nucleic acid sequences, aptamers, with direct signal detection via field-effect transistors (FETs). Aptamers can be designed for a range of target detection, signal transduction, response speed, and in vivo stability. Changes in biomolecular signaling molecule concentrations are monitored via optimized binding-induced aptamer conformation changes that are transduced into amplified electrical signals. For the small-molecule neurotransmitters serotonin and dopamine, aptamer FETs have limits of dection of 10 fM and retain their functionality in full ionic strength biological fluids including artificial cerebrospinal fluid and brain tissue. In other applications, we are able to "listen in" on the interspecies communications of signaling in competing populations in the microbiome.

Detecting single-nucleotide polymorphisms in DNA with ultrathin film field-effect transistors
Kevin Cheung^1,2, kevincheung@ucla.edu, John Abendroth^1,2, Nako Nakatsuka^1,2, Bowen Zhu^2,3, Yang Yang^2,3, Anne Andrews^1,4, Paul Weiss^1,2
1Chemistry & Biochemistry, University of California Los Angeles, Los Angeles, California, United States;
²California NanoSystems Institute, University of California Los Angeles, Los Angeles, California, United States;
³Materials Science and Engineering, University of California, Los Angeles, Los Angeles, California, United States;
⁴Psychiatry and Biobehavioral Health and Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, California, United States

Detecting single-nucleotide polymorphisms (SNPs) in oligonucleotides, related to a variety of diseases, for point-of-care applications necessitates the development of label-free electronic biosensors that can be easily translated into clinical settings. We have designed and fabricated functional biosensors using ultrathin film indium oxide field-effect transistors (FETs) that can differentiate target oligonucleotide strands with high sensitivity and selectivity. The semiconducting channels of the FETs are chemically functionalized with single-stranded DNA probes to test their selectivity towards complementary target sequences versus target strands that contain SNPs. Hybridization of negatively charged DNA significantly depletes semiconducting channels resulting in significant changes in current response. Modulation of channel conductance enables sensing DNA hybridization with detection limits of femtomolar concentrations. By taking advantage of the relative differences in stability of different base pair mismatches, we are investigating the ability of DNA-functionalized FETs to distinguish hybridization between fully complementary DNA sequences, and analogous sequences with different types and numbers of SNPs. We are advancing our system to detect SNPs, in both DNA and RNA sequences, under physiologically relevant conditions, and will continue to probe the limits of detection of the DNA-functionalized FETs. The development and implementation of biosensors that can sense and differentiate oligonucleotide sequences with SNPs at minute concentrations presents new opportunities in the fields of disease diagnostics and precision medicine.

Nanoscience Approaches to Heterogeneity in Biological Systems
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

The great promise of single-molecule/assembly measurements is to understand how critical variations in structure, conformation, and environment relate to and control function. New approaches to sensing, imaging, and analysis are keys to elucidating these associations. I will discuss current and upcoming advances and will pose the challenges that lie ahead in creating, developing, and applying new tools for biology and medicine. These advances include using biomolecular recognition in sensor arrays to probe dynamic chemistry in the brain and microbiome systems. It also includes fusing spectroscopic imaging modalities and freeing up bandwidth in measurements to record simultaneous data streams and to expand our dynamic range. Recent advances in sparsity and compressive sensing can be applied both to new analysis methods and to directing measurements so as to assemble and to converge structural and functional information. Early examples will be discussed.

Cage Molecule Self-Assembly
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

Upright, symmetric cage molecules self-assembled on surfaces have simple domain and defect structures. Unlike linear molecules, such as alkanethiols on Au{111}, these cage molecules do not tilt and do not conformationally relax. The lattices of the cage molecules are determined by the projections of the cages on the surface. Thus, different isomers, such as carboranethiols on Au{111}, form identical lattice structures. These monolayers enable key tests of simple phenomena, such as the effects of dipole moment direction and amplitude. For example, molecules with dipoles parallel to the surface form nonpolar monolayers and outcompete molecules with dipoles normal the surface, which form polar monolayers. These properties can be measured both at the macroscopic and nanoscopic scales. We understand the enhanced stability of the nonpolar surfaces to aligned dipoles in the monolayers and set out to measure such effects. Using combinations of spectroscopic imaging and novel image analyses based on advances in compressive sensing and sparsity, we find that dipoles do align, even across strcutural domain boundaries and step edges. We use mixed self-assembled monolayers of carboranes to tune and to optimize the band alignment of organic electronic devices without changing the morphology of the active layer. We assemble multifunctionalized cage molecules and show that we can protonate and deprotonate thiol(ate)s to change the valency of attachment to the surface through simple reactions. These experiments are closely coupled to theory and simulations to give us detailed understanding of the supramolecular systems.

Detecting single-nucleotide polymorphisms in DNA with ultrathin film field-effect transistors
Kevin Cheung^1,2, kevincheung@ucla.edu, John Abendroth^1,2, Nako Nakatsuka^1,2, Bowen Zhu^2,3, Yang Yang^2,3, Anne Andrews^1,4, Paul Weiss^1,2
1Chemistry & Biochemistry, University of California Los Angeles, Los Angeles, California, United States;
²California NanoSystems Institute, University of California Los Angeles, Los Angeles, California, United States;
³Materials Science and Engineering, University of California, Los Angeles, Los Angeles, California, United States;
⁴Psychiatry and Biobehavioral Health and Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, California, United States

Detecting single-nucleotide polymorphisms (SNPs) in oligonucleotides, related to a variety of diseases, for point-of-care applications necessitates the development of label-free electronic biosensors that can be easily translated into clinical settings. We have designed and fabricated functional biosensors using ultrathin film indium oxide field-effect transistors (FETs) that can differentiate target oligonucleotide strands with high sensitivity and selectivity. The semiconducting channels of the FETs are chemically functionalized with single-stranded DNA probes to test their selectivity towards complementary target sequences versus target strands that contain SNPs. Hybridization of negatively charged DNA significantly depletes semiconducting channels resulting in significant changes in current response. Modulation of channel conductance enables sensing DNA hybridization with detection limits of femtomolar concentrations. By taking advantage of the relative differences in stability of different base pair mismatches, we are investigating the ability of DNA-functionalized FETs to distinguish hybridization between fully complementary DNA sequences, and analogous sequences with different types and numbers of SNPs. We are advancing our system to detect SNPs, in both DNA and RNA sequences, under physiologically relevant conditions, and will continue to probe the limits of detection of the DNA-functionalized FETs. The development and implementation of biosensors that can sense and differentiate oligonucleotide sequences with SNPs at minute concentrations presents new opportunities in the fields of disease diagnostics and precision medicine.

Self-Collapse Lithography
Chuanzhen Zhao,¹ Xiaobin Xu,¹ Qing Yang,¹ Tianxing Man,² Steven J. Jonas,³ Jeffrey J. Schwartz,^1,4 Anne M. Andrews,^1,5 and Paul Weiss^1,6

(1) California NanoSystems Institute and Departments of Chemistry & Biochemistry, UCLA, Los Angeles, CA 90095, USA; (2) Department of Mechanical and Aerospace Engineering, UCLA, Los Angeles, CA 90095, USA; (3) Department of Pediatrics, David Geffen School of Medicine, Eli & Edythe Broad Center of Regenerative Medicine and Stem Cell Research, and Children's Discovery and Innovation Institute, UCLA, Los Angeles, CA 90095, USA; (4) Department of Physics and Astronomy, UCLA, Los Angeles, CA 90095, USA; (5) Department of Psychiatry and Biobehavioral Health, Semel Institute for Neuroscience and Human Behavior, and Hatos Center for Neuropharmacology, UCLA, Los Angeles, CA 90095, USA; (6) Department of Materials Science and Engineering, UCLA, Los Angeles, CA 90095, USA

In this work, we exploit a previously undesirable characteristic of soft lithography, namely roof-collapse, utilizing it to develop a facile and robust soft lithography technique for high-throughput nanoscale chemical patterning, called "self-collapse lithography". Nanoscale channels formed naturally at the edges of microscale relief features of elastomeric stamps were used to generate sub-30-nm features. A wide range of shapes (e.g., circles, squares, lines) and feature sizes (down to sub-30 nm) can be patterned by strategically designing stamp feature dimensions (such as shapes or depth) or by controlling Young's modulus. These chemical patterns can further serve as resists during selective etching process to pattern underlying materials such as gold. Finite element model simulations suggest a straightforward mechanism for the self-collapse process through competition between the restoring stress and adhesion stress along the gap edge of the stamp features. These simulation results correlate well with the experimental data and reveal the relationship between linewidths, channel heights, and the Young's moduli of the stamps. This work provides new insight into the natural propensity of elastomeric stamps to self-collapse and demonstrates a means of exploiting this behavior to achieve patterning via nanoscale chemical lift-off lithography.

Global Opportunities in Nanoscience and Nanotechnology
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

Two seemingly conflicting trends in nanoscience and nanotechnology are our increasing ability to reach the limits of atomically precise structures and our growing understanding of the importance of heterogeneity in the structure and function of molecules and nanoscale assemblies. By having developed the "eyes" to see, to record spectra, and to measure function at the nanoscale, we have been able to fabricate structures with precision as well as to understand the important and intrinsic heterogeneity of function found in these assemblies.

I will discuss the challenges, opportunities, and consequences of pursuing strategies to address both precision on the one hand and heterogeneity on the other. In our laboratories, we are taking the first steps to exploit precise assembly to optimize properties such as perfect electronic contacts in materials. We are also developing the means to make tens to hundreds of thousands of independent multimodal nanoscale measurements in order to understand the variations in structure and function that have previously been inaccessible in both synthetic and biological systems.

Another outcome of the development of our field has been our ability to communicate across fields. This skill that we develop in our students and colleagues has enhanced and accelerated the impact of nanoscience and nanotechnology on other fields, such as neuroscience and the microbiome. I will discuss the opportunities presented by these entanglements and give recent examples of advances enabled by nanoscience and nanotechnology.

Global Opportunities in Nanoscience and Nanotechnology
Paul S. Weiss, California NanoSystems Institute, UCLA, Los Angeles, CA 90095, USA/P>

Nanobiosensor arrays for multiplexed measurements of the spatiotemporal dynamics of neurotransmitters and microbiome signalomics
Paul S. Weiss^1,2,3 and Anne M. Andrews^1,2,4
1California NanoSystems Institute and Departments of ²Chemistry & Biochemistry, ³Materials Science & Engineering, and ⁴Psychiatry, UCLA, Los Angeles, CA 90095

Investigating multiplexed biochemical signaling requires sensitive and specific detection at the time and length scales of function. We couple the molecular recognition properties of rationally designed, chemically synthesized nucleic acid sequences, aptamers, with direct signal detection via field-effect transistors (FETs). Aptamers can be designed for a range of target detection, signal transduction, response speed, and in vivo stability. Changes in biomolecular signaling molecule concentrations are monitored via optimized binding-induced aptamer conformation changes that are transduced into amplified electrical signals. For the small-molecule neurotransmitters serotonin and dopamine, aptamer FETs have limits of dection of 10 fM and retain their functionality in full ionic strength biological fluids including artificial cerebrospinal fluid and brain tissue. In other applications, we are able to "listen in" on the interspecies communications of signaling in competing populations in the microbiome.

Global Opportunities in Nanoscience and Nanotechnology
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

Two seemingly conflicting trends in nanoscience and nanotechnology are our increasing ability to reach the limits of atomically precise structures and our growing understanding of the importance of heterogeneity in the structure and function of molecules and nanoscale assemblies. By having developed the "eyes" to see, to record spectra, and to measure function at the nanoscale, we have been able to fabricate structures with precision as well as to understand the important and intrinsic heterogeneity of function found in these assemblies.

I will discuss the challenges, opportunities, and consequences of pursuing strategies to address both precision on the one hand and heterogeneity on the other. In our laboratories, we are taking the first steps to exploit precise assembly to optimize properties such as perfect electronic contacts in materials. We are also developing the means to make tens to hundreds of thousands of independent multimodal nanoscale measurements in order to understand the variations in structure and function that have previously been inaccessible in both synthetic and biological systems.

Another outcome of the development of our field has been our ability to communicate across fields. This skill that we develop in our students and colleagues has enhanced and accelerated the impact of nanoscience and nanotechnology on other fields, such as neuroscience and the microbiome. I will discuss the opportunities presented by these entanglements and give recent examples of advances enabled by nanoscience and nanotechnology.

Global Opportunities in Nanoscience and Nanotechnology
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

Tutorial on Patterning across Scales
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095, USA

We place single molecules and assemblies into precisely controlled environments on surfaces. The inserted assemblies and the monolayer matrices that contain them can be designed so as to interact directly, to give stability or other properties to functional supramolecular assemblies. New families of highly symmetric molecules are being developed to yield even greater control and are enabling elucidation of the key design parameters of both the molecules and assemblies. These design elements, in turn, enable controlled chemical patterning from the sub-nanometer to the centimeter scales. We simultaneously develop metrology tools for these methods to give unprecedented insight on the structures, function, and properties of these assemblies.

Cooperative Function in Atomically Precise Nanoscale Assemblies
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095, USA

We use molecular design, tailored syntheses, intermolecular interactions, and selective chemistry to explore the ultimate limits of miniaturization. We direct molecules into desired positions to create nanostructures, to connect functional molecules to the outside world, and to serve as test structures for measuring single or bundled molecules. Interactions within and between molecules can be designed, directed, measured, understood, and exploited at unprecedented scales. Such interactions can be used to form precise molecular assemblies, nanostructures, and patterns, and to control and to stabilize function. We selectively test hypothesized mechanisms of function by varying molecular design, chemical environment, and measurement conditions to enable or to disable function and control using predictive and testable means. Critical to understanding these variations has been developing the means to make tens to hundreds of thousands of independent single-molecule/assembly measurements in order to develop sufficiently significant statistical distributions, while retaining the heterogeneity intrinsic in the measurements. We use a number of excitation mechanisms to induce changes in the molecules and assemblies, including electric field, light, electrochemical potential, ion binding, and chemistry. We measure the electronic coupling of the contacts between the molecules and substrates by measuring the polarizabilities of the connected functional molecules. We have likewise developed and applied the means to map buried chemical functionality and interactions. The next steps are to learn to assemble and to operate molecules together, both cooperatively and hierarchically, in analogy to biological muscles. We discuss our initial efforts in this area, in which we find both interferences and cooperativity.

Precise Chemical, Physical, and Electronic Nanoscale Contacts
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

The physical, electronic, mechanical, and chemical connections that materials make to one another and to the outside world are critical. Just as the properties and applications of conventional semiconductor devices depend on these contacts, so do nanomaterials, many nanoscale measurements, and devices of the future. We discuss the important roles that these contacts can play in preserving key transport and other properties. Initial nanoscale connections and measurements guide the path to future opportunities and challenges ahead. Band alignment and minimally disruptive connections are both targets and can be characterized in both experiment and theory. I discuss our initial forays into this area in a number of materials systems.

Analyzing Spin Selectivityin DNA-Mediated Charge Transfer
J. M. Abendroth, California NanoSystems Institute and Department of Chemistry & Biochemistry, UCLA, Los Angeles, CA 90095

Selective Promotion of Shewanella oneidensis Adhesion to Surfaces with Saccharide-Decorated RAFT Polymers
T. D. Young, California NanoSystems Institute and Department of Chemistry & Biochemistry, UCLA, Los Angeles, CA 90095

Glycopolymer Functionalization towards Control of Shewanella oneidensis Biofilm Formation
T. D. Young, California NanoSystems Institute and Department of Chemistry & Biochemistry, UCLA, Los Angeles, CA 90095

Fabrication of NanoVolcanos for Delivery of Gene-Editing Cargos to Immune Cells
Q. Yang, S. Hou, X. Xu, H.-R. Tseng, S. J. Jonas, and P. S. Weiss, Mattel Children's Hospital, California NanoSystems Institute, and Department of Chemistry & Biochemistry, UCLA, Los Angeles, CA 90095

Nanosubstrate-Mediated Delivery of Gene-Editing Materials
N. Wattanatorn, X. Xu, S. Hou, F. Wang, Q. Yang, M. Mastrodimos, H.-R. Tseng, S. J. Jonas, and P. S. Weiss, Mattel Children's Hospital, California NanoSystems Institute, and Department of Chemistry & Biochemistry, UCLA, Los Angeles, CA 90095

Guided Nanospears for Targeted and High Throughput Intracellular Gene Delivery
X. Xu, S. Hou, N. Wattanatorn, F. Wang, Q. Yang, C. Zhao, H.-R. Tseng, S. J. Jonas, and P. S. Weiss, Mattel Children's Hospital, California NanoSystems Institute, and Department of Chemistry & Biochemistry, UCLA, Los Angeles, CA 90095

Manufacturing Cellular Immunotherapies Using Sound
J. N. Belling, C. Zhao, A. Mendoza, L. K. Heidenreich, D. Stemer, S. J. Jonas, and P. S. Weiss, Mattel Children's Hospital, California NanoSystems Institute, and Department of Chemistry & Biochemistry, UCLA, Los Angeles, CA 90095

Scalable Artificial Blood Vessels for Manufacturing Cellular Therapies
J. N. Belling, L. K. Heidenreich, L. M. Kawakami, S. J. Jonas, and P. S. Weiss, Mattel Children's Hospital, California NanoSystems Institute, and Department of Chemistry & Biochemistry, UCLA, Los Angeles, CA 90095

Hydrodynamic Squeezing for Delivery of Genetic Material to Immune Cells
T. Young, M. Mellody, H. Munoz, S. J. Jonas, D. Di Carlo, and P. S. Weiss, Mattel Children's Hospital, California NanoSystems Institute, and Department of Chemistry & Biochemistry, UCLA, Los Angeles, CA 90095

Synthesis of Nanocarriers for Delivery of Gene-Editing Materials to Immune Cells
G. A. Vinnacombe, L. Scarabelli, S. J. Jonas, and P. S. Weiss, Mattel Children's Hospital, California NanoSystems Institute, and Department of Chemistry & Biochemistry, UCLA, Los Angeles, CA 90095

Detection of Circulating Tumor Cells using Gold Nanospikes in Microfluidic Channels
L. Scarabelli, L. K. Heidenreich, G. A. Vinnacombe, J. N. Belling, S. J. Jonas, and P. S. Weiss, Mattel Children's Hospital, California NanoSystems Institute, and Department of Chemistry & Biochemistry, UCLA, Los Angeles, CA 90095

Fabrication of Cell Deformation Microfluidic Devices with Slippery Liquid-Infused Porous Surfaces (SLIPS)
A. M. Mendoza, C. Zhao, I. Frost, S. J. Jonas, and P. S. Weiss, Mattel Children's Hospital, California NanoSystems Institute, and Department of Chemistry & Biochemistry, UCLA, Los Angeles, CA 90095

Cooperative Function in Atomically Precise Nanoscale Assemblies
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

Precise Chemical, Physical, and Electronic Nanoscale Contacts
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

Precise Chemical, Physical, and Electronic Nanoscale Contacts
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

Dave Allara's Legacy: Self-Assembly and Chemical Patterning across Scales
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

Self-Assembly and Chemical Patterning across Scales
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

We place single molecules and assemblies into precisely controlled environments on surfaces. The inserted assemblies and the monolayer matrices that contain them can be designed so as to interact directly, to give stability or other properties to functional supramolecular assemblies. New families of highly symmetric molecules are being developed to yield even greater control and are enabling elucidation of the key design parameters of both the molecules and assemblies. These design elements, in turn, enable controlled chemical patterning from the sub-nanometer to the centimeter scales. We simultaneously develop metrology tools for these methods to give unprecedented insight on the structures, function, and properties of these assemblies.

Precise Chemical, Physical, and Electronic Nanoscale Contacts
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

The physical, electronic, mechanical, and chemical connections that materials make to one another and to the outside world are critical. Just as the properties and applications of conventional semiconductor devices depend on these contacts, so do nanomaterials, many nanoscale measurements, and devices of the future. We discuss the important roles that these contacts can play in preserving key transport and other properties. Initial nanoscale connections and measurements guide the path to future opportunities and challenges ahead. Band alignment and minimally disruptive connections are both targets and can be characterized in both experiment and theory. I discuss our initial forays into this area in a number of materials systems.

Nanotechnology Approaches to Biological Heterogeneity and Cellular Therapies
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

The great promise of single-molecule/assembly measurements is to understand how critical variations in structure, conformation, and environment relate to and control function. New approaches to sensing, imaging, and analysis are keys to elucidating these associations. I will discuss current and upcoming advances and will pose the challenges that lie ahead in creating, developing, and applying new tools for biology and medicine. These advances include using biomolecular recognition in sensor arrays to probe dynamic chemistry in the brain and microbiome systems. It also includes fusing spectroscopic imaging modalities and freeing up bandwidth in measurements to record simultaneous data streams and to expand our dynamic range. Recent advances in sparsity and compressive sensing can be applied both to new analysis methods and to directing measurements so as to assemble and to converge structural and functional information. Early examples will be discussed.

Global Opportunities in Nanoscience and Nanotechnology
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

Two seemingly conflicting trends in nanoscience and nanotechnology are our increasing ability to reach the limits of atomically precise structures and our growing understanding of the importance of heterogeneity in the structure and function of molecules and nanoscale assemblies. By having developed the "eyes" to see, to record spectra, and to measure function at the nanoscale, we have been able to fabricate structures with precision as well as to understand the important and intrinsic heterogeneity of function found in these assemblies.

I will discuss the challenges, opportunities, and consequences of pursuing strategies to address both precision on the one hand and heterogeneity on the other. In our laboratories, we are taking the first steps to exploit precise assembly to optimize properties such as perfect electronic contacts in materials. We are also developing the means to make tens to hundreds of thousands of independent multimodal nanoscale measurements in order to understand the variations in structure and function that have previously been inaccessible in both synthetic and biological systems.

Another outcome of the development of our field has been our ability to communicate across fields. This skill that we develop in our students and colleagues has enhanced and accelerated the impact of nanoscience and nanotechnology on other fields, such as neuroscience and the microbiome. I will discuss the opportunities presented by these entanglements and give recent examples of advances enabled by nanoscience and nanotechnology.

Nanotechnology Approaches to Biological Heterogeneity and Cellular Therapies
Paul S. Weiss
California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

The great promise of single-molecule/assembly measurements is to understand how critical variations in structure, conformation, and environment relate to and control function. New approaches to sensing, imaging, and analysis are keys to elucidating these associations. I will discuss current and upcoming advances and will pose the challenges that lie ahead in creating, developing, and applying new tools for biology and medicine. These advances include using biomolecular recognition in sensor arrays to probe dynamic chemistry in the brain and microbiome systems. It also includes fusing spectroscopic imaging modalities and freeing up bandwidth in measurements to record simultaneous data streams and to expand our dynamic range. Recent advances in sparsity and compressive sensing can be applied both to new analysis methods and to directing measurements so as to assemble and to converge structural and functional information. Early examples will be discussed.

Understanding Energy Conversion at the Ultimate Limits of Miniaturization
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

Two seemingly conflicting trends in nanoscience and nanotechnology are our increasing ability to reach the limits of atomically precise structures and our growing understanding of the importance of heterogeneity in the structure and function of molecules and nanoscale assemblies. By having developed the "eyes" to see, to record spectra, and to measure function at the nanoscale, we have been able to fabricate structures with precision as well as to understand the important and intrinsic heterogeneity of function found in these assemblies.

I will discuss the challenges, opportunities, and consequences of pursuing strategies to address both precision on the one hand and heterogeneity on the other [1]. In our laboratories, we are taking the first steps to exploit precise assembly to optimize properties such as perfect electronic contacts in materials [2]. We are also developing the means to make tens to hundreds of thousands of independent multimodal nanoscale measurements in order to understand the variations in structure and function that have previously been inaccessible in both synthetic and biological systems [3,4].

Precise Chemical, Physical, and Electronic Nanoscale Contacts
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

Precise Chemical, Physical, and Electronic Nanoscale Contacts
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

The physical, electronic, mechanical, and chemical connections that materials make to one another and to the outside world are critical. Just as the properties and applications of conventional semiconductor devices depend on these contacts, so do nanomaterials, many nanoscale measurements, and devices of the future. We discuss the important roles that these contacts can play in preserving key transport and other properties. Initial nanoscale connections and measurements guide the path to future opportunities and challenges ahead. Band alignment and minimally disruptive connections are both targets and can be characterized in both experiment and theory. I discuss our initial forays into this area in a number of materials systems.

Analyzing Spin Selectivity in DNA-Mediated Charge Transfer via Fluorescence Microscopy
John M. Abendroth,^1,2 Nako Nakatsuka,^1,2 Matthew Ye,^1,2 Dokyun Kim,³ Eric E. Fullerton,³ Anne M. Andrews,^1,2,4 and Paul S. Weiss,^1,2,5
1California NanoSystems Institute, UCLA, Los Angeles, CA 90095
²Department of Chemistry & Biochemistry, UCLA, Los Angeles, CA 90095
³Department of Electrical and Computer Engineering, UCSD, La Jolla, CA
⁴Department of Psychiatry, UCLA, Los Angeles, CA 90095
⁵Department of Materials Science & Engineering, UCLA, Los Angeles, CA 90095

Aptamer Field-Effect Transistors Overcome Debye Length Limitations for In Vivo Small-Molecule Biosensing
Nako Nakatsuka, California NanoSystems Institute and Department of Chemistry & Biochemistry, UCLA, Los Angeles, CA 90095

Multifunctional Micro-/Nanomotors and Large Area 2D/3D Micro-/Nanofabrication
Xiaobin Xu, California NanoSystems Institute and Department of Chemistry & Biochemistry, UCLA, Los Angeles, CA 90095

Self-Assembly and Chemical Patterning across Scales
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

We place single molecules and assemblies into precisely controlled environments on surfaces. The inserted assemblies and the monolayer matrices that contain them can be designed so as to interact directly, to give stability or other properties to functional supramolecular assemblies. New families of highly symmetric molecules are being developed to yield even greater control and are enabling elucidation of the key design parameters of both the molecules and assemblies. These design elements, in turn, enable controlled chemical patterning from the sub-nanometer to the centimeter scales. We simultaneously develop metrology tools for these methods to give unprecedented insight on the structures, function, and properties of these assemblies.

Molecular Vibrational Nanoscopy: Chemical Imaging at the Nanoscale
Naihao Chiang, California NanoSystems Institute and Department of Chemistry & Biochemistry, UCLA, Los Angeles, CA 90095

Molecular Vibrational Nanoscopy: Chemical Imaging at the Nanoscale
Naihao Chiang, California NanoSystems Institute and Department of Chemistry & Biochemistry, UCLA, Los Angeles, CA 90095

Surprising Functionalization and Control of Cyanide on Au{111} and My Career in Science So Far
Kris Barr, California NanoSystems Institute and Department of Chemistry & Biochemistry, UCLA, Los Angeles, CA 90095

Nanotechnology Approaches to Cellular Therapies
Steven Jonas, California NanoSystems Institute and Department of Chemistry & Biochemistry, UCLA, Los Angeles, CA 90095

Precise Chemical, Physical, and Electronic Nanoscale Contacts
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

The physical, electronic, mechanical, and chemical connections that materials make to one another and to the outside world are critical. Just as the properties and applications of conventional semiconductor devices depend on these contacts, so do nanomaterials, many nanoscale measurements, and devices of the future. We discuss the important roles that these contacts can play in preserving key transport and other properties. Initial nanoscale connections and measurements guide the path to future opportunities and challenges ahead. Band alignment and minimally disruptive connections are both targets and can be characterized in both experiment and theory. I discuss our initial forays into this area in a number of materials systems.

Global Opportunities in Nanoscience and Nanotechnology
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

Two seemingly conflicting trends in nanoscience and nanotechnology are our increasing ability to reach the limits of atomically precise structures and our growing understanding of the importance of heterogeneity in the structure and function of molecules and nanoscale assemblies. By having developed the "eyes" to see, to record spectra, and to measure function at the nanoscale, we have been able to fabricate structures with precision as well as to understand the important and intrinsic heterogeneity of function found in these assemblies.

I will discuss the challenges, opportunities, and consequences of pursuing strategies to address both precision on the one hand and heterogeneity on the other. In our laboratories, we are taking the first steps to exploit precise assembly to optimize properties such as perfect electronic contacts in materials. We are also developing the means to make tens to hundreds of thousands of independent multimodal nanoscale measurements in order to understand the variations in structure and function that have previously been inaccessible in both synthetic and biological systems.

Another outcome of the development of our field has been our ability to communicate across fields. This skill that we develop in our students and colleagues has enhanced and accelerated the impact of nanoscience and nanotechnology on other fields, such as neuroscience and the microbiome. I will discuss the opportunities presented by these entanglements and give recent examples of advances enabled by nanoscience and nanotechnology.

Global Opportunities in Nanoscience and Nanotechnology
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

Two seemingly conflicting trends in nanoscience and nanotechnology are our increasing ability to reach the limits of atomically precise structures and our growing understanding of the importance of heterogeneity in the structure and function of molecules and nanoscale assemblies. By having developed the "eyes" to see, to record spectra, and to measure function at the nanoscale, we have been able to fabricate structures with precision as well as to understand the important and intrinsic heterogeneity of function found in these assemblies.

I will discuss the challenges, opportunities, and consequences of pursuing strategies to address both precision on the one hand and heterogeneity on the other. In our laboratories, we are taking the first steps to exploit precise assembly to optimize properties such as perfect electronic contacts in materials. We are also developing the means to make tens to hundreds of thousands of independent multimodal nanoscale measurements in order to understand the variations in structure and function that have previously been inaccessible in both synthetic and biological systems.

Another outcome of the development of our field has been our ability to communicate across fields. This skill that we develop in our students and colleagues has enhanced and accelerated the impact of nanoscience and nanotechnology on other fields, such as neuroscience and the microbiome. I will discuss the opportunities presented by these entanglements and give recent examples of advances enabled by nanoscience and nanotechnology.

Precise Chemical, Physical, and Electronic Nanoscale Contacts
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

The physical, electronic, mechanical, and chemical connections that materials make to one another and to the outside world are critical. Just as the properties and applications of conventional semiconductor devices depend on these contacts, so do nanomaterials, many nanoscale measurements, and devices of the future. We discuss the important roles that these contacts can play in preserving key transport and other properties. Initial nanoscale connections and measurements guide the path to future opportunities and challenges ahead. Band alignment and minimally disruptive connections are both targets and can be characterized in both experiment and theory. I discuss our initial forays into this area in a number of materials systems.

Nanoscience, Nanotechnology, and Beyond
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

The birth and development of the fields of nanoscience and nanotechnology have (uniquely) led to our ability to work and to communicate across fields. We have learned to share both problems and approaches. These skills have led to new approaches not only for our fields but for others. It is not accidental that nanoscientists have led the efforts worldwide to address problems in energy, water, security, medicine, neuroscience, the microbiome, and other areas. I will discuss how we can accelerate these efforts and leverage our skills to shape a safer, healthier world.

Global Opportunities in Nanoscience and Nanotechnology
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

Two seemingly conflicting trends in nanoscience and nanotechnology are our increasing ability to reach the limits of atomically precise structures and our growing understanding of the importance of heterogeneity in the structure and function of molecules and nanoscale assemblies. By having developed the "eyes" to see, to record spectra, and to measure function at the nanoscale, we have been able to fabricate structures with precision as well as to understand the important and intrinsic heterogeneity of function found in these assemblies.

I will discuss the challenges, opportunities, and consequences of pursuing strategies to address both precision on the one hand and heterogeneity on the other. In our laboratories, we are taking the first steps to exploit precise assembly to optimize properties such as perfect electronic contacts in materials. We are also developing the means to make tens to hundreds of thousands of independent multimodal nanoscale measurements in order to understand the variations in structure and function that have previously been inaccessible in both synthetic and biological systems.

Another outcome of the development of our field has been our ability to communicate across fields. This skill that we develop in our students and colleagues has enhanced and accelerated the impact of nanoscience and nanotechnology on other fields, such as neuroscience and the microbiome. I will discuss the opportunities presented by these entanglements and give recent examples of advances enabled by nanoscience and nanotechnology.

Leveraging Sparsity in Multimodal Nanoscale Imaging and Analyses
Paul S. Weiss,^1,2,3 Andrea Bertozzi,^1,4 and Stan Osher,^1,4,5,6,7
1California NanoSystems Institute and Departments of ²Chemistry & Biochemistry, ³Materials Science & Engineering, ⁴Mathematics, ⁵Computer Science, ⁶Electrical Engineering, and ⁷Chemical & Biomolecular Engineering, UCLA, Los Angeles, CA 90095

As most nanoscale imaging data are oversampled, significant opportunities exist in leveraging concepts, methods, and algorithms from compressive sensing and sparsity in recording data and assembling information efficiently. Thus, we have used nanoscale imaging as a testbed and driver for advances in imaging across all scales and modalities. Orders of magnitude expansions of dynamic range and accelerations of analyses are possible. We discuss early examples of successes in this area and point to how, with sufficiently fast algorithms, image acquisition and information assembly and convergence in nanoscience, microscopy, astronomy, reconnaissance, medicine, neuroscience, and entertainment could all be improved significantly. Nanoscale imaging tools, specifically scanning probe microscopies and spectroscopic imaging methods, are excellent testbeds for these studies both because of the programmability of acquisition and because of the relatively slow typical data acquisition rates.

This work was supported as part of the W. M. Keck Center for Leveraging Sparsity.

Nanotechnology Approaches to Cellular Therapies
Paul S. Weiss^1,2,3
1California NanoSystems Institute and Departments of ²Chemistry & Biochemistry and ³Materials Science & Engineering, UCLA, Los Angeles, CA 90095

We introduce biomolecular payloads into cells for gene editing at high throughput for off-the-shelf solutions targeting hemoglobinopathies, immune diseases, and cancers. We circumvent the need for viral transfection and electroporation, both of which have significant disadvantages in safety, throughput, cell viability, and cost. Mechanical deformation can make cell membranes transiently porous and enable gene-editing payloads to enter cells. These methods use specific chemical functionalization and control of surface contact and adhesion in microfluidic channels. Likewise, penetration of reproducibly nanomanufactured, loaded sharp features can introduce these packages into individual or many cells. We discuss our progress with these approaches and the methods that we use to quantify success.

Nanotechnology Approaches to Biological Heterogeneity and Cellular Therapies
Paul S. Weiss
California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

The great promise of single-molecule/assembly measurements is to understand how critical variations in structure, conformation, and environment relate to and control function. New approaches to sensing, imaging, and analysis are keys to elucidating these associations. I will discuss current and upcoming advances and will pose the challenges that lie ahead in creating, developing, and applying new tools for biology and medicine. These advances include using biomolecular recognition in sensor arrays to probe dynamic chemistry in the brain and microbiome systems. It also includes fusing spectroscopic imaging modalities and freeing up bandwidth in measurements to record simultaneous data streams and to expand our dynamic range. Recent advances in sparsity and compressive sensing can be applied both to new analysis methods and to directing measurements so as to assemble and to converge structural and functional information. Early examples will be discussed.

Heterogeneity of Structures of Biomolecular Assemblies without Averaging
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

In Honor of Stacey Bent: Self-Assembly across Substrates
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

Following the lead of Prof. Stacey Bent, we have worked to reproduce the advantages of and control available for self-assembly on coinage metal surfaces to technological surfaces. Accomplishing this goal would add the chemical dimension to nanolithography. One of the key challenges is removing surface passivation layers and preventing side reactions, such as oxides and oxidation, respectively, on group IV semiconducor surfaces. We describe our efforts in this controlled surface chemisryt. In addition, new families of highly symmetric molecules are being developed to yield even greater control and are enabling elucidation of the key design parameters of both the molecules and assemblies. These design elements, in turn, enable controlled chemical patterning from the sub-nanometer to the centimeter scales. We simultaneously develop metrology tools for these methods to give unprecedented insight on the structures, function, and properties of these assemblies.

Exploring the Ultimate Limits of Miniaturization
Paul S. Weiss, California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, UCLA, Los Angeles, CA 90095

The great promise of single-molecule/assembly measurements is to understand how critical variations in structure, conformation, and environment relate to and control function. New approaches to imaging and analysis are keys to elucidating these associations. I will discuss current and upcoming advances and will pose the challenges that lie ahead in creating, developing, and applying new tools for biology and medicine. These advances include fusing spectroscopic imaging modalities and freeing up bandwidth in measurements to record simultaneous data streams and to expand our dynamic range. Recent advances in sparsity and compressive sensing can be applied both to new analysis methods and to directing measurements so as to assemble and to converge structural and functional information. These efforts have opened the possibility of measuring the structures of biomolecular assemblies and ultimately associating variations in those structures and conformations with functional variations, as we ahve been able to for synthetic assemblies.

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