Nanoscale Sensing and Control of Biological Processes - Rapid progress with nanoelectronic components such as carbon nanotubes and metallic nanowires has made feasible the direct conversion of biological signals into electronic information. As this new field takes shape, the PI is testing the feasibility of nanoscale sensing and control of biological processes, such that a chip-scale component can be used to identify chemical species of interest, perform signal processing and computation based on the sensor inputs, and also electrochemically synthesize specified products in response. Major elements of this integrated nanoelectronic / microfluidic circuit concept have already been demonstrated in the PI’s laboratory and elsewhere. However, significant obstacles remain before real applications can be tested. One of the underlying unresolved scientific issues is how nanostructured electrodes behave differently from bulk electrodes — transport currents are significantly enhanced or suppressed due to local departures from electroneutrality. Although the behavior in principle can be modeled by solving the coupled Nernst-Planck and nonlinear Poisson equations, this process is difficult, slowly converging, and furthermore, the situations of experimental interest involve additional complexity, such as catalysts in solution and thin charged films due to organics adsorbed on the electrodes. In this research, nanoelectrodes will be configured and integrated with a microfluidic chip so that in situ nanoscale coupled electrochemical synthesis and detection can be conducted and then compared with a full physical model. The result will demonstrate the feasibility and procedures of predicting current-voltage behavior of nanoscale electrodes that are directly interfaced with biological systems.
We have recently discovered a family of novel organic catalysts for the ring-opening polymerization of cyclic esters to generate biodegradable and biocompatible polyesters. The most active catalysts are derived from stable N-heterocyclic carbenes. This project will involve the synthesis of new classes of organic catalysts and the evaluation of their behavior in the synthesis of novel polymer architectures.
Prerequisite: Prior lab experience (either in coursework or in research) a plus.
This project involves the use of characterization methods to define mechanisms in the organic catalytic degradation of polylactide (PLA). PLA is one of the most important synthetic biocompatible and biodegradable polymers with a wide range of biomedical, pharmaceutical, agricultural, and packing applications. The mechanical, physical and degradation properties are closely related to the stereochemistry of PLA, so sterocontrol of PLA homopolymers or copolymers is of utmost importance to achieve the desired features for applications. One of the important applications has a green chemistry affiliation: recycling of polyethyleneterephalate soft drink bottles.The intern on this project will work closely with postdoctorals and other interns in the polymer synthesis lab of James Hedrick (collaborating with Robert Waymouth’s lab), doing some synthesis but focusing on NMR and other methods which assist in learning about the mechanisms. The intern will learn advanced synthetic methods and dynamic NMR techniques. In addition, they will sit in on all group meetings which vary in topic from synthesis to physical measurements. Some references: Zhang, et al, Macromolecules 2007, 40, 4154-4158.
Thin films of block copolymers containing nanoscopic domains have merged as a promising patterning method for the creation of sub-optical lithographic features. This project involves computational molecular modeling of single molecule self-assembly, as well as the modeling of molecular systems of many small polymeric molecules to understand the phenomena of phase formation, defect formation, migration, and annealing. Student intern will be involved in performing molecular simulations and the analysis of resulting data sets. The intern’s work will also involve some computer programming, data analysis and statistics.
Prerequisite: Must be a chemistry or chemical engineering major and should have completed a course in physical chemistry. Student should be familiar with basic concepts of thermodynamics and statistical mechanics. Must have some basic computer programming skills, and experience with Unix and Windows.
Understanding the mechanisms of organo-catalytic polymerization reactions is an important aspect of polymer chemistry, and for many of these reactions there is no clear picture of the mechanism: Does it involve a radical intermediate? Is it a concerted reaction? What is the function of the catalyst? Does the solvent play an important role? The project uses computational chemistry methods to study these problems. A computational study of many possible reaction mechanisms helps elucidate the ones that may actually occur and to compare where possible with experimental data in the literature. In particular, we will investigate use of a variety of quantum mechanical methods and predict reactant/product structures, transition states and spectroscopic properties of the species involved. The intern’s work will involve some computer programming, quantum chemical calculation, molecular simulation, data analysis and statistics.
Prerequisite: Must be a chemistry or chemical engineering major and should have completed a course in physical chemistry. Student should be familiar with basic concepts of quantum mechanics. Must have some basic computer programming skills, and experience with Unix and Windows.
Understanding the underlying mechanisms of protein folding will have major impacts not just on biology and the life sciences but also on our ability to design similar nanostructured polymers. One simple model of the folding process is that it proceeds through the gradual accumulation of native-like intramolecular contacts until the native, fully folded conformation is reached. Simple statistical mechanical models based on this idea have been used to describe the observed folding behavior of several different proteins. This project will analyze some of the large protein simulation data sets from the Blue Gene project to see if atomistic simulations of the protein folding process can be used to produce Markov models. If such models accurately describe the behavior observed in the simulations, long time folding behavior can be deduced that conveys the rates of folding as well as the number and nature of the many folding pathways. In particular, we will look for characteristic patterns of secondary structure formation, as well as look to see if non-native contacts play any role in the folding process.
Prerequisite: Must have an interest in life sciences, physical chemistry or chemical engineering, computer simulation of biological molecules, or statistical mechanics. Student should have completed a course in physical chemistry. Must have some basic computer programming skills, and experience with Unix and Windows.
Mixed flows are hydrodynamic flows which contain varied levels of strain and vorticity. The ratio of these two very different flow types can create remarkable dynamics in soft matter objects that are intrinisic to biological processes. In this project we plan to examine the mixed flow dynamics of dsDNA molecules and vesicles, where the latter refers to small fluid sacs surrounded by functionalized bilayer membranes. Vesicles in shear flow, i.e. the exact balance between pure straining and pure vortical motion, are known to demonstrate tank-treading motion with a stationary shape, unsteady tumbling, and an oscillatory “breathing” mode depending on the excess area (relative to a sphere of the same volume), viscosity contrast between the inner and outer fluids, and the membrane bending rigidity. In mixed flows, dsDNA molecules have been predicted theoretically to undergo large length fluctuations as the shear flow limit is approached. The main questions we wish to address in these new studies are: 1) how do vesicle and dsDNA dynamics vary with flow type? 2) how does the introduction of integral membrane proteins or domains modify the dynamics of vesicles in mixed flows? 3) how do the viscosity contrast, membrane bending rigidity, domain line tension, surface microstructure, and integral membrane proteins affect the forces needed to rupture a vesicle? 4) how do these factors affect vesicle fusion? These questions will be addressed with a combination of large scale simulation using codes developed in the Shaqfeh research group, and fluorescence microscopy in a combined experimental effort between the Shaqfeh group (Stanford) and the Muller group (Berkeley). The latter will employ novel, new microfluidic “four roll mill” devices, developed by Muller and coworkers.
The integration of electrical function with the chemical principles of self-assembly is one of the most challenging problems in molecular electronics. Polydiacetylenes are a class of polymer which comprises a conjugated backbone with versatile side-group chemistry. By exploiting the molecular recognition principles of hydrogen bonding and hydrophobic-hydrophilic interactions in the substituents, diacetylene monomers can be synthesized and processed to form highly ordered monomolecular films, and subsequently polymerized topotactically by UV exposure. The resulting sheet of aligned polymer chains is then suitable to create the channel of a field-effect transistor. This project will involve the preparation of such polymer monolayers from monomers synthesized in the group of collaborator Robert Miller. Characterization of the morphology of films will be carried out using primarily optical and scanning-probe techniques. Electrical measurements of charge injection and transport will be made on field-effect transistor structures.
Prerequisite: Must have laboratory experience in the electrical and optical characterization of materials. 3rd and 4th year students will be given preference.
The goal of this project is to develop a process to deposit an ultra-thin dielectric on a polymeric thin-film transistor, which will act as a capacitive sensing layer.
The student will learn how to deposit high-k dielectrics by atomic layer deposition. The dielectric will encapsulate a polymeric transistor. By controlling the gate potential of the transistor, the device can operate as a sensor. The student will characterize polymeric transistors and verify the operational principles of the device. In addition to electrical characterization, the student will learn deposition techniques (spin-coating, atomic layer deposition) and atomic force microscopy as well as scanning electron microscopy.
The goal of this project is to control the synthesis of doped ZnO nanowires that can be used as a solution-processable electrode for organic photovoltaics.
The student will perfect the colloidal growth of ZnO nanowires by controlling synthesis temperature, time and presence of surfactants. The ZnO nanowires will be suspended in a solvent and spin-cast on glass substrates to form uniform films. The electrical properties of the films will be characterized as a function of synthesis and processing conditions. The student will use scanning electron microscopy to characterize the film morphology. Electrical and optical measurements will be performed as well. If successful, the project will culminate with the fabrication and characterization of an organic solar cell.
The goal of this project is to pattern the surface-energy of a substrate in order to spatially control the demixing of a blended semiconductor/dielectric solution.
The student will learn how to spatially pattern the hydrophobicity of a substrate. The spatially varying surface-energy will drive the decomposition of a semiconductor/dielectric via spin-coating to match the hydrophobicity pattern. By designing the pattern appropriately, an electric circuit will self-assemble where the semiconductor thin film will constitute the active areas and the dielectric will isolate the active areas. The student will characterize films by atomic force microscopy and scanning electron microscopy.
Biopolymers can have a number of useful materials properties, including well-defined nanoscale structure, specific binding interactions, and catalytic activity. To exploit these functions in solid phase materials, the biopolymers must be immobilized on a substrate or support. In this project, students will use computer simulations to study one of two biopolymer-surface systems: either polypeptides chemisorbed on a silicon substrate, where the influence of grafting density on the peptide structure will be explored; or folded DNA origami physisorbed on substrates of varying charge density, where the role of electrostatic interactions in the binding process will be examined.
Prerequisites: Must have completed a course in physical chemistry and be familiar with basic thermodynamics and statistical mechanics. Experience with computer programming is required.
As the current trend of creating smaller electronic devices continue, there is an increasing need to develop the materials and processes required to continue this trend. Emulating the assembly processes as they occur in Nature is one route to generating new materials for microelectronic devices that require particular attention to events as they occur at the nanoscale. We focus on using and understanding molecular recognition to control the self assembly of polymeric materials on surfaces. This includes employing controlled polymerization techniques to incorporate molecular functionalities into macromolecular architectures to control the manner by which they assemble.
The study of individual DNA molecules in microfluidic devices is of interest for both biological sequencing and detection applications and for the study of polymer conformation under hydrodynamic stresses. One project of current interest to our group is the development of sequence-specific probes for dsDNA such as duplex invasion using complimentary single stranded oligonucleotides. This will require the optimization of incubation procedures and the development of bulk detection techniques. The student researcher will gain experience in biological techniques, single molecule visualization, and characterization using fluorescence microscopy and spectrophotometry.
Prerequisite: Must be a biology, bioengineering, chemistry, or chemical engineering major.
The study of individual DNA molecules in microfluidic devices is of interest for both biological sequencing and detection applications and for the study of polymer conformation under hydrodynamic stresses. One project of current interest to our group is the development of multiple sequence-specific probes for dsDNA using restriction enzymes. This will require the identification of enzymes that bind sequence-specifically to dsDNA and determination of which conditions promote binding and prevent cleavage. The student researcher will gain experience in microfluidic device fabrication by soft lithography, biological techniques, and single molecule visualization and characterization using fluorescence microscopy.
Prerequisite: Must be a biology, bioengineering, chemistry, or chemical engineering major.
The need for clean, renewable energy to make a meaningful contribution to the world’s energy supply has never been more apparent. For photovoltaic solar power to have a large scale and long term impact, the cost of solar panels must be reduced without sacrificing much in the way of performance. Semiconductor nanocrystals, which are synthesized and processed at low temperature and in solution, offer a potential solution. Their optical properties have been demonstrated to be better even than thin film or crystalline silicon solar cell materials and the challenge is now to integrate them into films and into photovoltaic devices. We have an on-going project to develop the synthesis of new nanocrystals for solar cells and to integrate them into solar cell structures.
This summer’s intern will focus on the interface between nanocrystal thin films and the electrodes used to collect charge carriers generated by the solar cell. Applying different chemical conditions used for the deposition of nanocrystal thin films onto electrodes, the intern will apply fluorescence spectroscopy to characterize the resulting properties of the interface. Other materials characterization techniques, such as AFM and FTIR, will be used to understand the physical and chemical nature of the interface. Along the way, the intern will become acquainted with the synthesis and characterization of these advanced nanocrystal materials.
Block copolymers self assemble into a bewildering array of regular structures such as spheres, cylinders, lamellae, gyroids, diamond structures etc depending on the volumer percentage of the block copolymer and the respective interaction parameters between the blocks. Such structures can have very small features because of the molecular size of the respective phase separating blocks. This has provided the opportunity for sublithographic self assembly where the orientation of the features can be controlled by the surface energy of the substrate, the temperature, atmospheric composition etc. These features may be selectively reacted, metalized or removed to make a variety of nanostructures. The majority of physical studies on block copolymers have been done on a small number of readily available materials. Using synthetic controlled polymerization methods developed in the laboratory, access to a wide variety of functionalized block copolymer of unusual structure and morphologies can be envisioned. These in turn can be expected to spontaneously assembly into a variety of nanostructures for potential applications.
Prerequisite: Prefer a chemistry or chemical engineering major with some interest/experience with polymers.
Dendrimers are polymers with controlled sizes and shapes with abundant functionality on the periphery. Although the synthetic control is often excellent, the synthethesis and purification is tedious and time consuming. We have developed a synthetic procedure for the preparation of multiarm star polymer with excellent control of molecular weights, arm lengths and number, polydispersity and arm functionality. This anionic procedure is essential a simple one step procedure where the arm end functionality is introduced via the initiator. Various types of block copolymers can be generated by coupling the anionic with controlled radical procedures such as nitroxide mediated, atom transfer radical polymerization, RAFT etc to generate core-shell materials. The respective layers can be selectived crossinked if so desired. The project involves primarily synthesis and characterization of monomers and functional polymers for various applications such as nanoparticle synthesis, preparation of multiarm fluorophores, controlled reagent delivery, nanoscale reactors, photovoltaic systems, polymer crosslinking additives, etc.
Prerequisite: Prefer a chemistry or chemical engineering major with some interest/experience with polymers.
We are making a new type of low cost photovoltaic cell by patterning semiconducting polymers and inorganic semiconductors around each other at the nanometer length scale. Summer students will either develop techniques for self-assembling the nanostructures, study charge transport in polymer chains that are confined in nanopores, study exciton diffusion and energy transport in polymers or study how modifying the organic-inorganic interface affects electron transfer.
The major components of biological membranes (lipids) make biomedically useful nanometer-scale structures which will be explored in this project. For example, lipids self-assemble into: monolayers at an air-water interface, bilayers/vesicles in water, and supported bilayers on surfaces. The student will learn how to make the structure (e.g. supported lipid bilayer or microbubble), perform physical measurements (e.g. characterize microstructure) on the structure, and relate the measurements to a biomedically useful property (e.g. physiological function of a cell membrane or potential for use in drug delivery). These will be part of the ongoing effort in the Longo laboratory: http://www.chms.ucdavis.edu/research/web/longo/.
The Liu group has focused on using advanced nanofabrication methodologies to mimic the complexity of biomembranes. Using nanografting, an atomic force microscopy (AFM)-based nanofabrication method developed in the group, various nanostructures are produced to mimic cell membranes. These engineered surfaces can be used as supports for the formation of our biomimetic membrances to investigate if and how the underlying surface energy and functionality at nanoscal impact the resulting rafts size, structure, density, and dynamics. The concept of introducing nanoscale heterogeneity to supports is inspired by the complex structures at cytoskeleton of membrane and formation of functional complex within cell membranes. The ability to produce complex nanostructures is the first and critical step in the construction of useful nanoplatforms for the mimicking of membranes and the development of nanobiotechnology such as arrays of nanostructures of proteins and DNA molecules.
Prerequisite: Must be a chemistry or chemical engineering major.”
Membrane Proteins are investigated using electrochemically-controlled fluorescence spectroscopy down to the single molecule level. For this purpose, the proteins are immobilized in a strictly controlled orientation on a transparent indium/tin oxide (ITO) surface by the well-known his-tag technology. Subsequently they are reconstituted into a bilayer lipid membrane. These samples are then measured using a confocal microscope regarding their self-generated potential. This is done by adding potential sensitive fluorescent probes whose spectra change as a function of the membrane potential.
Tethered bilayer lipid membranes (tBLMs) are novel model architectures that mimic structure and function of natural biomembranes. The can be used to incorporate and study membrane proteins in a quasi natural, but well controlled environment.
During this project, the student will learn to prepare tethered membrane with newly synthesized molecules on gold substrates using various assembly techniques. He/she will characterize the optical (by Surface Plasmon Resonance Spectroscopy) and electrical parameters (by Impedance Spectroscopy) of the system. In a second step, we will use the model platform to study the interaction of proteins with the lipid bilayer. The interaction pathways for protein/membrane interactions are of importance e.g. for the design of novel antimicrobial peptides or to understand the function of membrane proteins.
Prerequisites: curiosity & interest in biophysical problems
Sum-frequency and second harmonic imaging techniques, which are based on nonlinear optical effects, will be used to image the spatial distribution of collagen macromolecular assemblies. The research involves the design and testing of new experimental concepts, as well as participating in the nonlinear optical measurements.
Advances in organometallic chemistry in the design and synthesis of single-site metal catalysts for olefin, ring-opening metathesis, and ring-opening polymerization techniques have enabled the preparation of well-defined functional polymeric materials with predictable molecular weights and narrow polydispersities. Surprisingly, relatively few polymerization reactions have been reported which employ simple organic molecules as reaction catalyst, despite the widespread availability of organic chemicals in enantiopure form. The ring-opening polymerization (ROP) of lactides, lactones and epoxides using nucleophilic organic catalysts such as amines, thiophenes, phosphines and imidizolidine carbenes has been investigated. The strategy employed for the ROP using organic catalysts is as follows. First, a nucleophile such as an alcohol must be used to initiate the polymerization of the cyclic monomer in the presence of the catalyst, which provides a means of molecular weight and end-group functionality control. Secondly, the ROP does not evolve a co-product and since the equilibrium is enthalpically driven, the equilibrium is prejudiced towards polymerization. Mild and highly selective polymerization conditions either in bulk or solution produced polymers with predictable molecular weights and extremely narrow polydispersities. New strategies for chiral and “planar-chiral” organocatalysts that enable the formation of highly enantioselective poly(lactides) and polyethers from racemic monomer mixtures will also be developed.
Macromolecular engineering has assumed increasing importance in polymer science. One approach to complex molecular architectures is through the preparation of block copolymers or two distinctive homopolymers covalently bound at one point. Another approach to complex molecular architectures is the introduction of controlled branching. The use of ring-opening polymerization (ROP) methods to develop such new architectures has been much less pervasive than other synthetic techniques. Our interest is in the ROP of lactones, lactides, etc. and other related monomers. This project will involve the synthesis of new biocompatible polymers with the object of tailoring elastomeric mechanical properties with new molecular architectures.
In this project, the stability of threads of oil floating on top of water will be studied. This problem is related to the phenomena of “dry eye”, where the tear film on the surface of the eye de-wets. Optical microscopy will be used to image the dynamics of these liquid threads and compare the results to theoretical descriptions of this process.
Molecular constructs with dimensions below a micrometer now appear frequently in research labs and in product applications, yet the properties of objects on this scale are not well understood. Often these nano-miniaturized structures behave differently than larger structures built from the same materials. This divergence is due to the limited number of molecules incorporated into the nanostructures and to their inhomogeneous environment. We study the behavior and control of organic interfaces as they are confined within the submicron length scale. The methods we use include lithographic and surface derivatization techniques, atomic force microscopy, and surface analysis to create and probe localized features and properties. The project often involves collaboration with biologists, synthetic chemists, and surface scientists to customize and analyze surfaces and materials.
Prerequisite: Must be adept at instrumentation and comfortable with chemicals.
This study will be directed toward the development of a diagnostic assay to monitor protein-lipid interactions. We will use the quartz crystal microbalance with dissipation to follow the kinetics of vesicle adsorption and subsequent vesicle fusion to form a planar supported lipid bilayer.
We are part of a large interdisciplinary collaboration with the Department of Ophthalmology in the Stanford School of Medicine whose goal is to create an artificial cornea. This SURE project will involve the synthesis and characterization of hydrogel networks that are candidate materials for the cornea.
The structure and function of human skin, and particularly the outermost layer of the skin, the stratum corneum (SC), are critical in maintaining bodily well being. Modifications to the SC such as by surfactants (e.g. soaps and detergents) can be detrimental to the lipids and proteins in the skin. By changing the SC microstructure, the mechanical properties of the SC are affected. This project seeks to connect the structure and mechanical properties of SC which are important for understanding SC function and for a range of emerging technologies such as transdermal drug delivery. Mechanical properties of SC will be explored by examining the affect of different treatments which cause specific changes to the tissue. Using a mechanics approach developed in our research group, the mechanical properties and intercellular delamination energy will be measured. Tissue will be treated with enzymes and other chemically active treatments to affect both the underlying cellular and intercellular structure and resulting mechanical function. Additional characterization will be conducted using solution diffusion techniques, scanning electron and optical microscopy.
This project develops novel nanowire and nanocrystal materials towards nanoscale electronics and energy conversion devices. Researchers will have an opportunity to learn about nanocrystal and nanowire synthesis, structure characterization, single nanostructure measurement, surface modification, self-assembly, device fabrication and testing. The exciting tools include scanning electron microscopy, transmission electron microscopy, X-ray diffraction, electron beam lithography, probe station and Langmuir-Blodgett.
Through an interdisciplinary collaboration within the Departments of Bioengineering, Chemical Engineering, and Ophthalmology, we aim to develop an artificial cornea that mimics the natural properties of the human cornea and allows for sustainable cell adhesion and growth. To achieve this goal, our team has created a novel hydrogel polymer as a base, and we are now incorporating proteins commonly found on the cornea onto this material. We will then assess the ability of cornea cells to function as they would naturally. We will look at the ability of the cells to attach to the hydrogel, and will measure their ability to grow, migrate, and express particular cell surface markers. A student would assist with these assays, primarily by helping to prepare the hydrogels for cell experiments and by helping to examine the function of the cells on the hydrogel by microscopy, cell surface marker detection, and single cell migration assays. The student will play an active role in designing and performing experiments, and they will have an opportunity to be exposed to many different scientific fields including: materials science, biology, biochemistry, and ophthalmology.
Due to Nature’s ability for self-recognition and assembly, a significant amount of research has focused at using biological systems to assemble nanoscale materials, such as nanoparticles, nanowires and carbon nanotubes. Recently, DNA based templates have garnered enormous interest due to their use as potential genetic “blueprints” for the directed placement of nanoscale materials. Currently we are developing methods to both direct the placement of individual DNA scaffolds on lithographically patterned substrates as well as use the DNA scaffolds to organize sub-10nm materials, such as metal or oxide nanoparticles. The focus of this particular project will be to investigate different chemical and biochemical approaches to interface these DNA bioscaffolds with various inorganic nanomaterials, including semiconductor and metallic nanparticles and nanowires. The summer research intern will learn collodial synthesis of metal and oxide nanoparticles, functionalization of nanoparticles and nanowires, bioconjugation and characterization. Another aspect of this research will be to investigate chemical methods for selectively nucleating metal or oxide growth on the DNA origami structures.
The structures of many components associated with biological membranes are known to atomic resolution. The organization of these components into more complex structures is less well known. We are involved in developing optical and mass spectrometry methods to probe this organization and dynamic changes in this organization. Summer projects involve a variety of strategies for labeling membrane-associated components for imaging applications.”
Organic electronics is an emerging field for next generation electronics. There are several applications of organic electronics including paper thin flexible displays, cheap radio frequency ID tags, and biological and chemical sensors. One of the major advantages or Organic (carbon based) electronics versus inorganic electronics is the ability to deposit organic electronic components from solution. Using solution processing, instead of the high priced processes used in conventional lithography necessary for inorganic technology, organic devices can be deposited from solutions using processes similar to those used in Newspaper printing industry.
The goal of this summer research project is to deposit a variety of organic semiconductors from solution and to optimize deposition conditions. Following deposition the organic transistors will be tested for electrical performance. The ultimate goal is then to elucidate how solution deposition conditions affect thin film properties which ultimately determine how well current flows in the organic transistor. More specifically the student researcher will be involved in surface science experiments including functionalization chemistry of surfaces, preparation and deposition of solutions of organic semiconductors, and testing electrical performance using a probe station. Students will learn about how transistors, the building block electronic devices, work as well as the new exciting field of organic electronics.