Eric SG Shaqfeh - US grants

This research by a Presidential Young Investigator is focused on several thrusts in the area of fluid flow with complex, non- Newtonian fluids. The approach is both theoretical/numerical and experimental. The areas are: composites, polymer melts, and suspensions; viscoelastic instabilities; and material transport characteristics. In addition, layer phenomena related to plasma etching and bilayer lithography are included in the research plans. Impact of the research will be on improved process control for superior material characteristics involving electronic materials and solid fiber composites.

This award will support collaborative research between Dr. George Homsy, Department of Chemical Engineering, Stanford University and Dr. Elisabeth Guazelli, Ecole Superieure de Physique et Chimie Industrielles, Paris, France. The objective of the project is to investigate the hydrodynamics of fluid particle systems. The investigators will study hydrodynamic effects in suspensions and fluidized beds. The behavior of such dispersed multiphase systems is important in a number of fields of science and technology. These include applications in handling and processing materials such as: 1) composites and emulsions, 2) chemical processing of fluids, as in fluidized bed reactors, 3) environmental fluid mechanics, such as sediment and nutrient transport in natural flows and 4) separation technologies, such as flotation, sedimentation and clarification. Despite intensive study of these fields over the last several decades, there are many fundamental aspects of the mechanical behavior of such systems that remain poorly understood, in particular, the interactions between the particles making up the dispersed phase. In this project, the investigators propose to carry out: 1) theoretical and numerical studies of hydrodynamic interactions between particles in suspension, and 2) experimental studies of the behavior of sedimenting suspen- sions, fluidized beds, and so-called "ferro fluids", i.e. suspensions of magnetic Brownian particles. The primary focus of the French group will be the experimental studies, while that of the US will be theoretical and numerical modeling. The project will benefit from the availability of special NMR facilities for flow visualization in the French laboratory.

ABSTRACT Proposal Number: CTS-9731896 Principal Investigator: Shaqfeh This is a grant to address a number of important problems in the study of polymer rheology that can be characterized as non-continuum or non-local. These are typically associated with the influence of boundaries or constrained environments on the stress-strain rate relationship. The burgeoning interest in these problems arises from the growing need to process materials at the molecular level. In most cases, new physical principles need to be applied to such problems because the most fundamental relationships, e.g. the relationship between the tension along a molecular backbone and the average extra stress in the mixture, need to be derived anew. Moreover these highly constrained flow fields are now only beginning to be experimentally interrogated, but the early data suggests that qualitatively new Theological behavior needs to be understood in these cases. Three problems that can serve as paradigms for theoretical model-building have been selected for study: a) the Couette-Poiseuille flow of flexible chains in solution when the pore or channel thickness is comparable to the radius of gyration of the polymers, b) the bulk shearing flow of polymer solutions near a boundary where the interface may contain adsorbed or grafted polymer layers, and c) the squeeze flow lubrication of "wet" polymer brush covered surfaces. The technique will be used is a novel hybrid scheme involving self-consistent flow calculations using HP adaptive finite elements and large scale Brownian dynamics simulations of bead-rod (Kramer's) chains.

Abstract
CTS-0090428
E. Shaqfeh, Stanford University

This is one of two identical proposals submitted by Washington University and Stanford University. A combined experimental and numerical study is proposed to examine the effect of elasticity on the stability of fluid-fluid displacement interfaces-sometimes known as the "ribbing" instability. Such instabilities limit either the speed or the quality of production of adhesive coatings in industrial processes. This is a collaborative effort between Bamin Khomami of Washington University and Eric Shaqfeh of Stanford University with the numerical part being carried out mainly in the former institution while the experimental part mainly at the latter institution. Preliminary experiments performed by the PI's showed the dramatic onset of such instabilities. It is hypothesized that the instability is caused by the unstable stress gradient created by the extensional finger flow near the displacing front. The research plan is to obtain quantitative experimental data of such instability flows using modern instrumentation, to carry out linear and nonlinear stability analysis of the flows, and full three-dimensional simulations of the unstable elastic fluid interfaces to test the hypothesis. In addition, the possibility of enhancing the stability of the system by introducing time-periodic parametric forcing will be examined by simulations.

PROPOSAL NO.: CTS-0522564
PRINCIPAL INVESTIGATOR: E.S.G. SHAQFEH
INSTITUTION: STANFORD UNIVERSITY


Recent collaborative work in the PI's research group has demonstrated, that the coil-stretch transition in an extensional flow is a "first order" transition, a topic that had been debated for 30 years. In this transition there is a region of conformation hysteresis where two kinetically separated conformation states can exist at the same value of the dimensionless stretching rate. This is a direct consequence of intra-chain hydrodynamic interactions. The modeling of the rheology of such a material requires a new paradigm. Under this grant the researchers will use a large-scale computer simulation, projection methods from statistical mechanics, and single molecule DNA experiments to develop the elements of such a paradigm. In particular, Brownian dynamics simulations will be developed to study the kinetic processes that are principle to understanding conformation hysteresis: the kinetics of the unraveling (transition from coiled-unravelled), the kinetics of the collapse (from the extended to the coiled state), and the kinetics of fluctuation induced "hopping" between the extended and coiled-states in the hysteretic regime. Different flow types will be studied, including planar mixed flows, three dimensional linear flows, and nonlinear flows, that demonstrate new characteristics of this conformation hysteresis. The combination of large-scale simulation and single molecule experiments provides a powerful tool that will allow the researchers to examine this new paradigm in polymer solution rheology. The study of conformation hysteresis and conformational phase transitions in solution rheology is in its infancy and thus the full broad impact of these new ideas is not completely apparent. It is already clear that in many instances the state of stress in a solution is dependent on enormous time scales associated with the time history of the molecules in these hysteretic states, especially in microfluidics contexts. The proposed work has broader impacts in terms of training, and teaching undergraduate and graduate students a new way of thinking about the dynamics of molecules in flow. Through this project, graduate students and undergraduate students will be trained in this multidisciplinary research that involves fluid mechanics, microfabrication and materials processing, and numerical methods. Prof. Shaqfeh engages in outreach programs already through the CPIMA materials center, which include giving seminars at colleges for under-represented groups. Teaching infrastructure will be enhanced through the development of web-based modules for introducing high school students to DNA dynamics, methods for manipulating DNA using flow, and for calculating forces on large molecules. These will be based on visualization movies of the DNA from the experiments and the simulation codes, both of which will be made available on the Internet.

This project aims to synthesize metal-organic semiconducting molecule-metal structures with nanoscale metallic contacts pre-assembled or templated by DNAs, or directly connected to the molecule as chemisorbed gold nanoparticles/nanowires. The metallic contacts will form ohmic contacts to molecular devices for circuits from DC to microwave frequencies. Precisely fabricated, ultrasmall gaps are not needed since the overall hybrid structure will be much longer than the organic molecule of interest. At optical frequencies, the metallic contacts will form an electromagnetic cavity around the molecular device, enhancing optical fields to be utilized in single-molecule spectroscopic measurements. Self-assembly of these new nanoscale objects will be investigated both theoretically and experimentally. Electrical devices will be fabricated to study charge transport through single molecules. New electrical, optical and physical phenomenon may arise from these unique nanoscale structures. The open planar geometry formed in this work is expected to allow electrostatic modification of electronic states using a nearby strongly-coupled gate electrode, and will reduce fluorescence quenching by nearby metallic electrodes. Single-molecule based transistors and light-emitting diodes may be generated from the proposed structures. The methods developed will lay the groundwork for developing molecular electronic and optical devices and integrating them into complex circuits.
Intellectual Merit. Fundamental advances across disciplines are essential to the advancement of nanoscale devices and to understanding their behavior. Molecular synthesis, self-assembly, and charge transport are essential components for realizing nanoscale devices with organic molecules. A coordinated team attack on such issues can advance the state of single-molecule devices. This project will be carried out by a team of two chemists, one solid-state physicist, one spectroscopist, and one theorist together with collaborators from industry, national labs, and foreign universities with expertise in polymer synthesis, surface chemistry, biochemistry, DNA self-assembly, DNA metallization, spectroscopy, charge transport, fluid dynamics simulation, and device fabrication.
Broader Impacts. This project may result in a new approach to make electrical contacts to single molecules, which will allow study of charge transport through single molecules with different chemical functionalities and length as well as measurement of unique optical properties arising from a single molecule confined in a nanogap. The proposed work will not only answer fundamental questions of intramolecular charge transport mechanisms in molecules with length scale of 5-100 nm, it will also provide answers to technological questions of whether organic molecules have sufficient performance for nanoelectronics and whether the mobility of molecular devices will be dramatically increased by alignment of organic semiconducting molecules between electrodes. This project also utilizes methods to self- assemble DNA-polymer-DNA and nanoparticle-molecule-nanoparticle structures using electrophoresis and dielectrophoresis to allow electrical connections to be made to single organic semiconducting molecules. The PIs will work closely with existing NSF centers and the Stanford Office of Science Outreach to reach a broad population ranging from K-12, community college, undergraduate, and graduate students as well as to prepare teachers of tomorrow for new areas of science and technology. Two internship positions every year for minority and/or women community college students are integral to the project. One research position per year will also be provided to a middle school or high school teacher during the summer; PIs will continue to work with them to develop their education plans after their summer research. PIs will also reach out to the general public through a public website and participation in various community events. The graduate students and postdoc involved in the project will actively interact with each other and have the opportunity to interact with researchers from industry, national labs, and international collaborators. They will be well equipped with a combination of technical engineering skills, basic scientific understanding, and communication skills, and poised to contribute to nanoscience and nanotechnology.

National Science Foundation - Division of Chemical &Transport Systems ? Particulate & Multiphase Processes Program (1415)

Proposal Number: 0729771
Principal Investigators: Shaqfeh, Eric
Affiliation: Stanford
Proposal Title: Experimental and Computational Design of a Microfluidic Device for
Micro-Barcode Based Oligonucleotide Synthesis


Micro-barcode technologies have the potential to realize large-scale multiplexing of hundreds of thousands of biochemical reactions in a single reaction vessel. Microarrays, which perform large-scale multiplexing on two-dimensional substrates, have transformed biomedical research by enabling genome wide investigation of genetic variation and function. Micro-barcode particles are poised to translate this capability to a three-dimensional, free-solution format, greatly expanding the possibilities of this powerful technology. Rod-shaped metallic particles with 0.25 to 1 micron diameters and lengths of 2 to 10 microns (Nanoplex, Menlo Park, CA) can be grown with metallic stripes that encode on the order of 10 bits of information. Each micro-barcode particle carries an identifiable signature, analogous to a conventional barcode, that serves as a mechanism for tracking molecular probes, such as oligonucleotides, attached to the particle surface. Many such particles then be mixed, reacted with a sample, and detected in parallel in a single chamber or fluidic channel. We propose to develop an automated particle flow control, electricfield alignment, sorting, and readout technology applicable to massively-parallel oligonucleotide synthesis. We will build and demonstrate custom-designed microfluidic devices, that for the first time, will control, read, and sort micro-barcode particles in microfluidic systems. Critical to the device design and optimization, will be the development of generalized electro-kinetic models that account for particle Brownian motion, electrophoresis (including mono- and multi-pole electrokinetic effects), hydrodynamic forces, and sedimentation in confined geometries. These models will be in the form of large-scale multi-particle simulations using novel numerical codes being developed jointly with the experiments. The large-scale simulations will allow us to accurately predict the location, velocity and orientation of the particles as they travel through the device, and thus quantitatively predict device performance.

We have performed preliminary experiments in which we align and subsequently track the positions and orientations of cylindrical particles 5 microns long and 0.25 microns in diameter under settling conditions in both DC and AC electric fields. In additional to the initial experiments, we have already developed simulation tools to model the sedimentation of a large number of Brownian rods at low Reynolds number with electrophoretic alignment and particle-induced electrophoretic flow in periodic systems, thus determining the initial flow parameter regimes that we will ultimately examine in detail. The broader research impact and intellectual merit of our work includes a fundamental understanding of a number of unsolved problems in suspension mechanics which directly bear on the performance of these barcode readers. These issues include developing our understanding of (a) the rheology of rod-like polymer and rod-like colloidal particle suspensions from dilute through semi-dilute including ICEP interactions; (b) the effect of ICEP flow on the collective phenomena associated with the simultaneous sedimentation and mean flow of fiber suspensions; (c) the action of shear-induced diffusion on the center of mass motion of the rod-like particles; and (d) the collective dynamics of rod suspensions in non-local flows, i.e. those in which the mean flow scale is on the order of the length of the rod. Indeed, even though these principles are intrinsic to the science of the microfluidics of complex fluids, many of the combinations of these nonlinear physics will be examined for the first time. Moreover, the broad educational impact associated with using large scale computing for design of microfluidic devices will be developed as an integral part of two summer internships for high school science teachers via a partnership with Stanford's Summer Research Program for Science Teachers. These internships will include faculty at one or two Title I schools. One internship will be associated with the experimental aspects of the research and the other with the computational design aspects. The internships will allow the faculty members to work closely with the PIs and graduate students and form a working group to understand the applications of microfluidic technology and advanced computing as an engineering design tool, and thereafter take experimental expertise, demonstrations and computer simulations back to the classroom.

[unreadable] DESCRIPTION (provided by applicant): Current methods for determining Single Nucleotide Polymorphisms (SNPs) on chromosomal DNA require either microarrays (Affymetrix, Inc. - http://www.affymetrix.com/index.affx; Perlegen Sciences -- http://www.perlegen.com/) or single molecule combing techniques combined with optical gene mapping (OpGen, Inc. -- http://www.opgen.com). These methods, in general, distinguish perhaps a few hundred SNPs on a single chromosome in a given test and do not produce true haplotype information over more than 1Kbp. Moreover, DNA sequencing and microarray technologies are limited by the slow process of DNA hybridization. We propose to use recent advances in the isolation and stretch of single, large DNA molecules in flow devices, particularly stagnation point flows, to develop a rapid, single molecule, genomic sequencing (SNP and tag SNP) technology based on sequence- specific hybridization to probes bound to fluorescent beads. This new microfluidic process has the potential to revolutionize SNP genotyping by revealing thousands of SNPs in a few scans and reducing processing times to a few hours (per thousand SNPs). As the public HapMap project reveals, there are as many as 300K tag SNPs in the human genome. Thus, the primary question that we pose: Is it possible to develop a single molecule method to complete a full genomic scan by exploiting microfluidic manipulation of the DNA? To address this question, we require an understanding of the coupling between hydrodynamics and the dynamics of DNA molecules, the kinetics of hybridization reactions, and the molecular biology techniques associated with hybridization probe development. We propose to demonstrate the techniques to accomplish this by developing these methods on ?-phage DNA, concatemers of ? - phage DNA, T4 as well as E. Coli DNA with the latter including genomic lengths in excess of 1 Mbp. We propose to develop the techniques to accomplish a complete tag SNP scan of an organism's genome, including the human genome, using single molecule techniques in microfluidics. A complete tag SNP scan of the human genome, accomplished inexpensively and in a few days, sets the stage for the era of personalized medicine. Genome wide association studies for medicine including early prediction of genetic tendencies for disease as well as genomic predispositions to drug response can become widely used, with the resulting enormous impact on the field of pharmacogenomics. [unreadable] [unreadable] [unreadable]

DESCRIPTION (provided by applicant): DNA sequencing is currently in the midst of disruptive technological shifts, with 454, Illumina, and Solid providing us with enormous throughput increases and large reductions in cost per base. Massively parallel technologies deliver a few Gbp of sequence per week as short fragments, or reads. New applications of sequencing only recently considered impractical are enabled: personal genome sequencing, "metagenomics" analysis of 'soups'containing several, to hundreds of unique organisms, and finally, de novo sequencing of novel genomes of complex organisms. No matter how the sequencing is done, reads must be assembled computationally, if they are to be useful. Given the read length and read quality limitations of new instruments and the massive volume of data generated, the computational assembly problem is becoming critical, with the cost of computational infrastructure and personnel exceeding reagent and instrument-related costs. Moreover, the results of assembly are currently far from ideal;for example, much of the human genome remains invisible due to high percentage of repeats. We propose to develop a new "front end" to next-gen sequencers for DNA preparation, the "Read-Cloud Method", which can reduce computational cost of genome assembly by 2-3 orders of magnitude, produce more complete and accurate genomes, and make metagenomics tractable. We propose a hierarchical sequencing approach, without any need for bacterial cloning. We will achieve this by handling single DNA molecules, tiled across the genome with high redundancy, on microfluidic devices. We will design, prototype, and thoroughly test technology to (i) shear genomic DNA into 200- kbp fragments with narrow size distributions;(ii) randomly amplify each individual, 200-kbp DNA in isolation, within a porous gel microcontainer that will be formed around the dsDNA molecule within a microdevice;(iii) digest micro-encapsulated DNA into small fragments, of tunable size;(iv) bar-code the progeny of each 200-kbp DNA with a 12mer oligonucleotide, to identify each read as associated with a particular 200-kbp DNA. A planar microfluidic device will be fabricated to allow one unique bar- code sequence to be blunt-end-ligated to both DNA termini. Bar-coded DNA is pooled, and next-gen sequencing is done. The results are a highly reducible data set. The method and algorithm are applicable universally, to next-generation platforms. The PIs (Batzoglou, Barron, Shaqfeh, Quake) will collaborate to make an efficient approach to hierarchical sequencing in microfluidic devices. PUBLIC HEALTH RELEVANCE: Project Narrative Gene sequencing is important to medicine. Our DNA sequencing method has the potential for reducing computational cost by orders of magnitude while making the assembled genomes significantly more complete and accurate. The key to this step is using microfluidic handling technologies to subdivide genomic DNA into 200kbp fragments, which are then amplified in isolation from each other and uniquely-labeled to form a highly reducible dataset for genomic assembly.

0960306
Shaqfeh

"This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5)."

This proposal is for the acquisition of a high performance, Hybrid CPU/GPU and Visualization Cluster (HPVC) that is designed to serve the needs of 7 working groups where each is involved in HPC research to solve problems of large global and national impact. The unique aspects of the HPVC cluster lies, in the combination of state-of-the art computer visualization, enhanced performance with large datasets via GPU architecture, and the development of computational uncertainty quantification (UQ). These elements, , will be employed in the solution of interdisciplinary, multiphysics transport problems including (a) engineering Nutrient Transport in Oceanographic Coral Reef Flows (to protect our environment and save the reefs), (b) the Development of Trauma and Nanoparticle Cancer Therapies including understanding hemostasis in the microcirculation (impacting human health), (c) Modeling the Dispersion of Biological Agents in Urban Environments (for Homeland Security), (d) using Quantum Chemistry to Design Catalysts for Fuel Cells (toward sustainable energy development), (e) simulating the Molecular Dynamics of Proteins and the Ribosome (for understanding the basic processes of life), (f) developing a fundamental understanding of Jet Noise Creation (to develop effective noise mitigation strategies for jets, fans, etc.), and finally, (g) to create algorithms for Design Optimization for Sustainable Building Development (as a contribution toward the larger issue of sustainability). The HPVC will play a key role in education, via bringing CPU with GPU enhanced acceleration to the classroom in a spectrum of Stanford courses as well as new workshops on GPU computing. The concept of Uncertainty Quantification as applied to large scale HPC problems will be introduced via a new UQ pipeline as a novel software deliverable within the HPVC research program.

Award: 1066263
PI: Shaqfeh/Muller

This project represents a comprehensive investigation of the individual dynamics and the collective interactions of vesicles, capsules, and capsule/particle mixtures. The collaborative research is a synergistic effort between high performance computer (HPC) simulations of multiphase flow phenomena as well as detailed experiments using microfluidics and microrheology. Novel aspects of the simulation algorithm include a smooth particle mesh Ewald boundary element code employing both spectral, Loop subdivision, and boundary element resolution of the deforming and interacting interfaces. Essentially, arbitrary shear, bending, and dilatational moduli in the interfacial modeling can be included thus allowing the full range of dynamics from capsules to vesicles including rigid particles and mixtures to be simulated in complex microfluidic geometries. Moreover, nonBrownian and Brownian suspensions can be simulated with high resolution of the interfaces. The experiments include direct visualization, via fluorescence microscopy, of the detailed time varying dynamics of vesicles, and, by creative interfacial chemistry, capsules with varying shear modulus in (a) the microfluidic four roll mill device (capable of reproducing any planar mixed flow in the vicinity of a stagnation point at which the vesicle/capsule may be trapped and observed for extended times) and (b) microchannel geometries designed for examination of collective suspension dynamics. Experiments will also focus on measurements, through fluorescence microscopy and particle tracking, of the shear-induced diffusion of particles and the rheological behavior as the confinement length scale is varied. Applications including understanding platelet hemostasis in the microcirculation as well as engineering vesicles for medical applications.

1337051
PI: Shaqfeh

Suspensions of rigid particles in viscoelastic fluids play key roles in many energy applications, materials design applications, and consumer product applications. For example, in oil drilling the so-called drilling mud is a very viscous, viscoelastic fluid designed to shear-thin during drilling, but thicken at stoppage so that the cuttings can remain suspended. In a related application known as hydraulic fracturing (an operation used to stimulate petroleum and gas production) suspensions of solids called proppant are used to prop open the fracture by pumping them into the well. Quality performance of the proppant demands placement deep into the fracture requiring that the excess weight of the solids be supported during the flow. A commonly used proppant-transport liquid is an aqueous guar polymer solution, transiently cross-linked with borate ion, such that it is highly elastic. It is well known that the sedimentation of particles in a viscoelastic fluid can be quite different from that which is observed in Newtonian fluids, especially under shear. For example, in a non-Newtonian liquid, the complex rheological properties induce a nonlinear coupling between the sedimentation and shear flow which is not found in Newtonian liquids and which is critical to the function of the aforementioned drilling and fracking fluids. In a related materials application, the cleaning of particulate matter from surfaces, particularly in applications associated with etching of silicon wafers is often done by a post processing known as rinse. Most recently, it has been shown that a viscoelastic solution becomes a far more effective rinse agent than a Newtonian solution, even at the same viscosity. Again, in this application, the elasticity in a flowing, sheared fluid seems to change, in a manner as yet unknown, the forces on particulates subject to gravity in directions orthogonal to the shear flow, creating thereby an enhanced lift force that cleans the surface.

In this project, the research team will develop large scale, computer simulations of particle suspensions at finite concentration in viscoelastic fluids. The focus will be on particles acted on by a body force (i.e. gravity) as well as an applied shear flow in a direction orthogonal to gravity with the goal of understanding the applications described above. The computer simulations will be unique, first of their kind, combining unstructured, finite volume technology with immersed boundary techniques in elastic liquids. Such simulations are, in the authors view, the only known way to understand the nonlinear physics in these highly nonequilibrium flow applications and thus to engineer these fluids rather than develop them based on historical precedent.

The movement of micro-organisms is often complicated by the complexity of the fluids in which they reside. Many of the fluids (e.g., mucous) in which these organisms “swim” contain large macromolecules such as proteins that limit successful swimming. It is more difficult to swim through these “sticky” fluids. It has recently been suggested theoretically that a type of microbial swimming called “swirl” can create propulsion in complex liquids that would not be possible in “simple,” less sticky fluids. Swirl is characterized by parts of the body spinning around the axis of an axisymmetric body. Swirl is a key feature of the swim stroke of many micro-organisms. This award will develop a novel micro-robot that demonstrates the characteristics of swirl propulsion in complex fluids and uses that propulsion to measure the properties of the surrounding fluid. Thus, it is a dynamic sensor of complex fluid properties or a “swimming rheometer”.

Standard rheometers are desktop devices where fluid is brought to the device and the native environment of the fluid application is reproduced in the device. The state of stress in the shear flow of complex fluids requires the measurement of at least three material properties as a function of the shear rate in the fluid. The goal in the present award is that through design, miniaturization, and optimization of a newly developed “swirling” robot, rheometry will be transformed to a remote, in situ sensing science. Thus, one will bring the “rheometer to the fluid application” rather than bringing a fluid sample to a fixed rheometer. A tennis ball-size prototype has already been created and the primary concepts are successfully demonstrated. The robot was designed and will continue to be optimized via large scale computer simulation. The miniaturized robot will have immediate medical and biological applications including measuring the complex rheological properties of synovial fluid as a direct mapping to several disease conditions. Moreover, multiple miniaturized robots will be used to examine the collective dynamics of these micro-swirlers.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.