George M. Whitesides

Harvard University, Cambridge, Massachusetts, United States

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Publications (788)6523.86 Total impact

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    ABSTRACT: This paper presents methods that use Magnetic Levitation (MagLev) to measure very small differences in density of solid diamagnetic objects suspended in a paramagnetic medium. Previous work in this field has shown that, while it is a convenient method, standard MagLev (i.e., where the direction of magnetization and gravitational force are parallel) cannot resolve differences in density < 10-4 g/cm3 for macroscopic objects (> mm) because i) objects close in density prevent each other from reaching equilibrium height due to hard contact and excluded volume, and ii) using weaker magnets or reducing the magnetic susceptibility of the medium destabilizes the magnetic trap. The present work investigates the use of weak magnetic gradients parallel to the faces of the magnets as a means of increasing the sensitivity of MagLev without destabilization. Configuring the MagLev device in a rotated state (i.e., where the direction of magnetization and gravitational force are perpendicular) relative to the standard configuration enables simple measurements along the axes with the highest sensitivity to changes in density. Manipulating the distance of separation between the magnets or the lengths of the magnets (along the axis of measurement) enables the sensitivity to be tuned. These modifications enable an improvement in the resolution up to 100 over the standard configuration, and measurements with resolution down to 10-6 g/cm3. Three examples of characterizing the small differences in density among samples of materials having ostensibly indistinguishable densities-Nylon spheres, PMMA spheres, and drug spheres-demonstrate the applicability of rotated Maglev to measuring the density of small (0.1-1 mm) objects with high sensitivity. This capability will be useful in materials science, separations, and quality control of manufactured objects.
    No preview · Article · Jan 2016 · Analytical Chemistry
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    ABSTRACT: Nerve growth factor (NGF) promotes growth, differentiation and survival of sensory neurons in the mammalian nervous system. Little is known about how NGF elicits faster axon outgrowth or how growth cones integrate and transform signal input to motor output. Using cultured mouse dorsal root ganglion neurons, we found that myosin II (MII) is required for NGF to stimulate faster axon outgrowth. From experiments inducing loss or gain of function of MII, specific MII isoforms, and vinculin-dependent adhesion-cytoskeletal coupling, we determined that NGF causes decreased vinculin-dependent actomyosin restraint of microtubule advance. Inhibition of MII blocked NGF stimulation, indicating the central role of restraint in directed outgrowth. The restraint consists of myosin IIB- and IIA-dependent processes: retrograde actin network flow and transverse actin bundling, respectively. The processes differentially contribute on laminin-1 and fibronectin due to selective actin tethering to adhesions. On laminin-1, NGF induced greater vinculin-dependent adhesion-cytoskeletal coupling that slowed retrograde actin network flow (i.e., it regulated the molecular clutch). On fibronectin, NGF caused inactivation of myosin IIA that negatively regulated actin bundling. On both substrates, the result was the same: NGF-induced weakening of MII-dependent restraint led to dynamic microtubules entering the actin-rich periphery more frequently, giving rise to faster elongation.
    Preview · Article · Dec 2015 · Molecular biology of the cell
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    ABSTRACT: This work examines charge transport (CT) through self-assembled monolayers (SAMs) of oligoglycines having an N-terminal cysteine group that anchors the molecule to a gold substrate, and demonstrate that CT is rapid (relative to SAMs of n-alkanethiolates). Comparisons of rates of charge transport-using junctions with the structure AuTS/SAM//Ga2O3/EGaIn (across these SAMs of oligoglycines, and across SAMs of a number of structurally and electronically related molecules) established that rates of charge tunneling along SAMs of oligoglycines are comparable to that along SAMs of oligophenyl groups (of comparable length). The mechanism of tunneling in oligoglycines is compatible with superexchange, and involves interactions among high-energy occupied orbitals in multiple, consecutive amide bonds, which may by separated by one to three methylene groups. This mechanistic conclusion is supported by density functional theory (DFT).
    No preview · Article · Dec 2015 · Angewandte Chemie International Edition
  • Ana C Glavan · Jia Niu · Zhen Chen · Firat Güder · Chao-Min Cheng · David R Liu · George M Whitesides
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    ABSTRACT: This paper addresses a growing need in clinical diagnostics for parallel, multiplex analysis of biomarkers from small biological samples. It describes a new procedure for assembling arrays of ssDNA and proteins on paper. This method starts with the synthesis of DNA oligonucleotides covalently linked to paper, and proceeds to assemble microzones of DNA-conjugated paper into arrays capable of simultaneously capturing DNA, DNA-conjugated protein antigens, and DNA-conjugated antibodies. The synthesis of ssDNA oligonucleotides on paper is convenient and effective, with 32% of the oligonucleotides cleaved and eluted from the paper substrate being full-length by HPLC for a 32-mer. These ssDNA arrays can be used to detect fluorophore-linked DNA oligonucleotides in solution, and as the basis for DNA-directed assembly of arrays of DNA-conjugated capture antibodies on paper, detect protein antigens by sandwich ELISAs. Paper-anchored ssDNA arrays with different sequences can be used to assemble paper-based devices capable of detecting DNA and antibodies in the same device, and enable simple microfluidic paper-based devices.
    No preview · Article · Nov 2015 · Analytical Chemistry
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    ABSTRACT: This work describes the adaptive use of conventional stainless steel pins-used in unmodified form or coated with carbon paste-as working, counter, and quasi-reference electrodes in electrochemical devices fabricated using cotton thread or embossed omniphobic R(F) paper to contain the electrolyte and sample. For some applications, these pin electrodes may be easier to modify and use than printed electrodes, and their position and orientation can be changed as needed. Electroanalytical devices capable of multiplex analysis (thread-based arrays or 96-well plates) were easily fabricated using pins as electrodes in either thread or omniphobic R(F) paper.
    No preview · Article · Nov 2015 · Lab on a Chip
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    ABSTRACT: Soft, pneumatic actuators that buckle when interior pressure is less than exterior provide a new mechanism of actuation. Upon application of negative pneumatic pressure, elastic beam elements in these actuators undergo reversible, cooperative collapse, and generate a rotational motion. These actuators are inexpensive to fabricate, lightweight, easy to control, and safe to operate. They can be used in devices that manipulate objects, locomote, or interact cooperatively with humans, as described by G. M. Whitesides and co-workers on page 6323.
    Preview · Article · Nov 2015 · Advanced Materials
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    ABSTRACT: It is well known that 3D in vitro cell cultures provide a much better model than 2D cell cultures for understanding the in vivo microenvironment of cells. However, significant technical challenges in handling and analyzing 3D cell cultures remain, which currently limits their widespread application. Herein we demonstrate the application of wholly synthetic thermo-responsive block copolymer worms in sheet-based 3D cell culture. These worms form a soft, free-standing gel reversibly at 20-37 °C, which can be rapidly converted into a free-flowing dispersion of spheres on cooling to 5 °C. Functionalization of the worms with disulfide groups was found to be essential for ensuring sufficient mechanical stability of these hydrogels to enable long-term cell culture. These disulfide groups are conveniently introduced via statistical copolymerization of a disulfide-based dimethacrylate under conditions that favour intramolecular cyclization and subsequent thiol/disulfide exchange leads to the formation of reversible covalent bonds between adjacent worms within the gel. This new approach enables cells to be embedded within micrometer-thick slabs of gel with good viability, permits cell culture for at least 12 days, and facilitates recovery of viable cells from the gel simply by incubating the culture in buffer at 37 °C (thus avoiding the enzymatic degradation required for cell harvesting when using commercial protein-based gels such as Matrigel).
    No preview · Article · Oct 2015 · Biomacromolecules
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    ABSTRACT: Soft, pneumatic actuators that buckle when interior pressure is less than exterior provide a new mechanism of actuation. Upon application of negative pneumatic pressure, elastic beam elements in these actuators undergo reversible, cooperative collapse, and generate a rotational motion. These actuators are inexpensive to fabricate, lightweight, easy to control, and safe to operate. They can be used in devices that manipulate objects, locomote, or interact cooperatively with humans.
    No preview · Article · Sep 2015 · Advanced Materials
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    DESCRIPTION: This paper describes the design and fabrication of ion-sensing electrochemical paper-based analytical devices (EPADs) in which a miniaturized paper reference electrode is integrated with a small ion-selective paper electrode (ISPE) for potentiometric measurements. Ion-sensing EPADs use printed wax barriers to define electrochemical sample and reference zones.
    Full-text · Research · Aug 2015
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    ABSTRACT: This paper demonstrates that, for applications in resource-limited environments, expensive microplate spectrophotometers-which are used in many central laboratories for parallel measurement of absorbance of samples-can be replaced by photometers based on inexpensive and ubiquitous, consumer electronic devices (e.g., scanners and cell-phone cameras). Two devices-i) a flatbed scanner operating in transmittance mode and ii) a camera-based photometer constructed from a cell phone camera, a planar light source, and a cardboard box-demonstrate the concept. These devices illuminate samples in microtiter plates from one side, and use the RGB-based imaging sensors of the scanner/camera to measure the light transmitted to the other side. The broadband absorbance of samples (RGB-resolved absorbance) can be calculated using the RGB color values of only three pixels per micro-well. Rigorous theoretical analysis establishes a well-defined relationship between the absorbance spectrum of a sample and its corresponding RGB-resolved absorbance. The linearity and precision of measurements performed with these low-cost photometers on different dyes that absorb across the range of the visible spectrum, and chromogenic products of assays (e.g., enzymatic, ELISA) demonstrates that these low-cost photometers can be used reliably in a broad range of chemical and biochemical analyses. The ability to perform accurate measurements of absorbance on liquid samples, in parallel and at low cost, would enable testing, typically reserved for well-equipped clinics and laboratories, to be performed in circumstances where resources and expertise are limited.
    No preview · Article · Aug 2015 · Analytical Chemistry
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    ABSTRACT: This work describes a 3D, paper-based assay that can isolate sub-populations of cells based on their invasiveness (i.e., distance migrated in a hydrogel) in a gradient of concentration of oxygen (O2). Layers of paper impregnated with a cell-compatible hydrogel are stacked and placed in a plastic holder to form the invasion assay. In most assays, the stack comprises a single layer of paper containing mammalian cells suspended in a hydrogel, sandwiched between multiple layers of paper containing only hydrogel. Cells in the stack consume and produce small molecules; these molecules diffuse throughout the stack to generate gradients in the stack, and between the stack and the bulk culture medium. Placing the cell-containing layer in different positions of the stack, or modifying the permeability of the holder to oxygen or proteins, alters the profile of the gradients within the stack. Physically separating the layers after culture isolates sub-populations of cells that migrated different distances, and enables their subsequent analysis or culture. Using this system, three independent cell lines derived from A549 cancer cells are shown to produce distinguishable migration behavior in a gradient of oxygen. This result is the first experimental demonstration that oxygen acts as a chemoattractant for cancer cells. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Full-text · Article · Jun 2015 · Biomaterials
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    William H Bloxham · Jonathan W Hennek · Ashok A Kumar · George M Whitesides
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    ABSTRACT: This paper describes a method of isolating small, highly accurate density-standard beads and characterizing their densities using accurate and experimentally traceable techniques. Density standards have a variety of applications, including the characterization of density gradients, which are used to separate objects in a variety of fields. Glass density-standard beads can be very accurate (± 0.0002 g cm-3), but are too large (3-7 mm in diameter) for many applications. When smaller density standards are needed, commercial polymer microspheres are often used. These microspheres have standard deviations in density ranging from 0.006 to 0.021 g cm-3; these distributions in density make these microspheres impractical for applications demanding small steps in density. In this paper, commercial microspheres are fractionated using aqueous multiphase systems (AMPS)-aqueous mixture of polymers and salts that spontaneously separate into phases having molecularly sharp steps in density-to isolate microspheres having much narrower distributions in density (standard deviations from 0.0003 to 0.0008 g cm-3) than the original microspheres. By reducing the heterogeneity in densities, this method reduces the uncertainty in the density of any specific bead and, therefore, improves the accuracy within the limits of the calibration standards used to characterize the distributions in density.
    Full-text · Article · Jun 2015 · Analytical Chemistry
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    George M Whitesides
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    ABSTRACT: ‘Bioinspiration’—using phenomena in biology to stimulate research in non-biological science and technology—is a strategy that suggests new areas for research. Beyond its potential to nucleate new ideas, bioinspiration has two other interesting characteristics. It can suggest subjects in research that are relatively simple technically; it can also lead to areas in which results can lead to useful function more directly than some of the more familiar areas now fashionable in chemistry. Bioinspired research thus has the potential to be accessible to laboratories that have limited resources, to offer routes to new and useful function, and to bridge differences in technical and cultural interactions of different geographical regions.
    Preview · Article · May 2015 · Interface focus: a theme supplement of Journal of the Royal Society interface
  • Ashok A Kumar · Jenna A Walz · Mathieu Gonidec · Charles R Mace · George M Whitesides
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    ABSTRACT: Combining aqueous multiphase systems (AMPS) and magnetic levitation (MagLev) provides a method to produce hybrid gradients in apparent density. AMPS-solutions of different polymers, salts, or surfactants that spontaneously separate into immiscible but predominantly aqueous phases-offer thermodynamically stable steps in density that can be tuned by the concentration of solutes. MagLev-the levitation of diamagnetic objects in a paramagnetic fluid within a magnetic field gradient-can be arranged to provide a near-linear gradient in effective density where the height of a levitating object above the surface of the magnet corresponds to its density; the strength of the gradient in effective density can be tuned by the choice of paramagnetic salt and its concentrations, and by the strength and gradient in the magnetic field. Including paramagnetic salts (e.g., MnSO4 or MnCl2) in AMPS, and placing them in a magnetic field gradient, enables their use as media for MagLev. The potential to create large steps in density with AMPS allows separations of objects across a range of densities. The gradients produced by MagLev provide resolution over a continuous range of densities. By combining these approaches, mixtures of objects with large differences in density can be separated and analyzed simultaneously. Using MagLev to add an effective gradient in density also enables tuning the range of densities captured at an interface of an AMPS by simply changing the position of the container in the magnetic field. Further, by creating AMPS in which phases have different concentrations of paramagnetic ions, the phases can provide different resolutions in density. These results suggest that combining steps in density with gradients in density can enable new classes of separations based on density.
    No preview · Article · May 2015 · Analytical Chemistry
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    ABSTRACT: Die universitäre Forschung an Point-of-Care-Diagnostik für die globale Gesundheit verzeichnet ein stetes Wachstum, allerdings verlassen viele Testsysteme niemals das Labor. Prozesse, die die diagnostische Technologie vom Labor ins Feld überführen – Prozesse, mit deren Hilfe Betrieb und Leistungsvermögen unter realistischen Bedingungen evaluiert werden sollen –, sind komplizierter, als sie scheinen mögen. Zwei Fallstudien illustrieren diesen Prozess: die Entwicklung eines papierbasierten Testsystems zur Messung der Leberfunktion sowie die eines Testsystems zur Identifikation von Sichelzellanämie, das auf wässrigen, mehrphasigen Systemen sowie Unterschieden in der Dichte normaler und sichelförmiger Zellen beruht. Aus den Details der Entwicklung dieser beiden Testsysteme lassen sich allgemeingültige Strategien zum Aufbau von Kooperationen, zum Herstellen von Prototypen, zur Validierung, zum Design von Studien und zur Evaluation von Point-of-Care-Diagnostik ableiten. Die aus diesen Erfahrungen gezogenen (verfahrens)technischen Lehren können Wissenschaftlern nutzen, die diagnostische Tests für Entwicklungsländer und – allgemeiner – Technologien für den Einsatz bei begrenzten Ressourcen entwerfen.
    No preview · Article · Apr 2015 · Angewandte Chemie
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    ABSTRACT: Despite the growth of research in universities on point-of-care (POC) diagnostics for global health, most devices never leave the laboratory. The processes that move diagnostic technology from the laboratory to the field-the processes intended to evaluate operation and performance under realistic conditions-are more complicated than they might seem. Two case studies illustrate this process: the development of a paper-based device to measure liver function, and the development of a device to identify sickle cell disease based on aqueous multiphase systems (AMPS) and differences in the densities of normal and sickled cells. Details of developing these devices provide strategies for forming partnerships, prototyping devices, designing studies, and evaluating POC diagnostics. Technical and procedural lessons drawn from these experiences may be useful to those designing diagnostic tests for developing countries, and more generally, technologies for use in resource-limited environments. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    Preview · Article · Apr 2015 · Angewandte Chemie International Edition
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    ABSTRACT: Charge transport through junctions consisting of insulating molecular units is a quantum phenomenon that cannot be described adequately by classical circuit laws. This paper explores tunneling current densities in self-assembled monolayer (SAM)-based junctions with the structure AgTS/O2C‒R1‒R2‒H//Ga2O3/EGaIn, where AgTS is template-stripped silver, and EGaIn is the eutectic alloy of gallium and indium; R1 and R2 refer to two classes of insulating molecular units-(CH2)n and (C6H4)m-that are connected in series and have different tunneling decay constants in the Simmons equation. These junctions can be analyzed as a form of series tunneling junctions based on the observation that permuting the order of R1 and R2 in the junction does not alter the overall rate of charge transport. By using the Ag/O2C interface, this system decouples the HOMO (which is localized on the carboxylate group) from strong interactions with the R1 and R2 units. The differences in rates of tunneling are thus determined by the electronic structure of the groups R1 and R2; these differences are not influenced by the order of R1 and R2 in the SAM. In an electrical potential model that rationalizes this observation, R1 and R2 contribute independently to the height of the barrier. This model explicitly assumes that contributions to rates of tunneling from the AgTS/O2C and H//Ga2O3 interfaces are constant across the series examined. The current density of these series tunneling junctions can be described by J(V) = J0(V)exp(-β1d1 - β2d2), where J(V) is the current density (A/cm2) at applied voltage V, and βi and di are the parameters describing the attenuation of the tunneling current through a rectangular tunneling barrier, with width d and a height related to the attenuation factor β.
    No preview · Article · Apr 2015 · Journal of the American Chemical Society
  • Dataset: ja4075776

    No preview · Dataset · Mar 2015
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    ABSTRACT: Die Badische Anilin- & Sodafabrik – die BASF – wurde am 6. April 1865 von Friedrich Engelhorn in Mannheim gegründet und wird damit in diesem Jahr 150 Jahre alt. Das vorliegende Heft bietet anlässlich dieses besonderen Firmenjubiläums eine Sammlung von Aufsätzen und Essays, die sich mit Beiträgen der Chemie zu den Themen Energie, Ernährung und städtisches Leben befassen. Woher wird die Energie in Zukunft kommen, die wir brauchen? Wie können genug Nahrung und sauberes Wasser für alle Menschen bereit gestellt werden? Wie werden die Städte der Zukunft aussehen? Passend dazu sind auf dem Titelbild einige Highlights aus der breiten Produktpalette der BASF herausgestellt: Kathodenmaterialien für Lithium-Ionen-Batterien (oben), Membranen für sauberes Wasser (unten) sowie Xemium®, ein neuer fungizider Wirkstoff. Dieses Heft begleitet drei BASF-Jubiläumssymposien in Ludwigshafen (9./10. März), Chicago (23./24. Juni) und Shanghai (10./11. November), bei denen Autoren dieses Heftes vortragen. Es wird eingeleitet von einem Essay von A. Kreimeyer et al. auf S. 3220 ff. über die Geschichte und aktuelle Position der Forschung der BASF, worauf ein Essay von G. M. Whitesides auf S. 3238 ff. folgt, in dem er zu einem Umdenken in der chemischen Forschung aufruft. Alle zwanzig Essays und Aufsätze dieses Heftes demonstrieren die enorme Bedeutung chemischer Forschung – sie muss und wird zur Hebung des durchschnittlichen Lebensstandards einer wachsenden Weltbevölkerung beitragen. Die Redaktion der Angewandten Chemie gratuliert der BASF zu ihrem Jubiläum.
    No preview · Article · Mar 2015 · Angewandte Chemie
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    Kung-Ching Liao · Carleen M Bowers · Hyo Jae Yoon · George M Whitesides
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    ABSTRACT: This paper describes the influence of substitution of fluorine for hydrogen on the rate of charge transport through junctions of the form AgTSO2C(CH2)n(CF2)mT//Ga2O3/EGaIn, where T is methyl (CH3) or trifluoromethyl (CF3). Alkanoate-based self-assembled monolayers (SAMs) having perfluorinated groups (RF) show current densities that are lower (by factors of 20-30) than those of the homologous hydrocarbons (RH), while the attenuation factors of the simplified Simmons equation for methylene (β =1.05 ± 0.02 nCH2-1) and difluoromethylene (β =1.15 ± 0.02 nCF2-1) are similar. A comparative study focusing on the terminal fluorine substituents in SAMs of omega-tolyl and -phenyl alkanoates suggests that the C-F//Ga2O3 interface is responsible for the lower tunneling currents for CF3. The decrease in the rate of charge transport in SAMs with RF groups (relative to homologous RH groups) is plausibly due to an increase in the height of the tunneling barrier at the T//Ga2O3 interface, and/or to weak van der Waals interactions at that interface.
    Full-text · Article · Mar 2015 · Journal of the American Chemical Society

Publication Stats

82k Citations
6,523.86 Total Impact Points


  • 1983-2015
    • Harvard University
      • Department of Chemistry and Chemical Biology
      Cambridge, Massachusetts, United States
  • 2012
    • Stanford University
      • Department of Electrical Engineering
      Palo Alto, California, United States
  • 2004
    • California Institute of Technology
      • Gates and Crellin Laboratories of Chemistry
      Pasadena, California, United States
  • 1998
    • Case Western Reserve University
      • Department of Chemical Engineering
      Cleveland, Ohio, United States
  • 1967-1992
    • Massachusetts Institute of Technology
      • • Department of Materials Science and Engineering
      • • Department of Chemistry
      Cambridge, Massachusetts, United States
  • 1985
    • Idenix Pharmaceuticals, Inc.
      Cambridge, Massachusetts, United States
  • 1975
    • Cornell University
      Итак, New York, United States