George M. Whitesides

Harvard University, Cambridge, Massachusetts, United States

Are you George M. Whitesides?

Claim your profile

Publications (804)6398.9 Total impact

  • Source
    [Show abstract] [Hide abstract]
    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.
    Biomaterials 06/2015; 52. DOI:10.1016/j.biomaterials.2015.02.012 · 8.31 Impact Factor
  • [Show abstract] [Hide abstract]
    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.
    Angewandte Chemie 04/2015; DOI:10.1002/ange.201411741
  • [Show abstract] [Hide abstract]
    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.
    Angewandte Chemie International Edition 04/2015; DOI:10.1002/anie.201411741 · 11.34 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Dissipative colloidal materials use energy to generate and maintain structural complexity. The energy injection rate, and properties of the environment are important control parameters that influence the outcome of dynamic self-assembly. Here we demonstrate that dispersions of magnetic microparticles confined at the air-liquid interface, and energized by a uniaxial in-plane alternating magnetic field, self-assemble into a variety of structures that range from pulsating clusters and single-particle-thick wires to dynamic arrays of spinners (self-assembled short chains) rotating in either direction. The spinners emerge via spontaneous breaking of the uniaxial symmetry of the energizing magnetic field. Demonstration of the formation and disaggregation of particle assemblies suggests strategies to form new meso-scale structures with the potential to perform functions such as mixing and sensing.
    Scientific Reports 03/2015; 5:9528. DOI:10.1038/srep09528 · 5.08 Impact Factor
  • Source
    Dataset: ja4075776
  • Angewandte Chemie 03/2015; 127(11). DOI:10.1002/ange.201590010
  • [Show abstract] [Hide abstract]
    ABSTRACT: This paper uses the binding pocket of human carbonic anhydrase II (HCAII, EC as a tool to examine the properties of Hofmeister anions that determine (i) where, and how strongly, they associate with concavities on the surfaces of proteins and (ii) how, upon binding, they alter the structure of water within those concavities. Results from X-ray crystallography and isothermal titration calorimetry show that most anions associate with the binding pocket of HCAII by forming inner-sphere ion pairs with the Zn2+ cofactor. In these ion pairs, the free energy of anion-Zn2+ association is inversely proportional to the free energetic cost of anion dehydration; this relationship is consistent with the mechanism of ion pair formation suggested by the "Law of Matching Water Affinities." Iodide and bromide anions also associate with a hydrophobic declivity in the wall of the binding pocket. Molecular dynamics simulations suggest that anions, upon associating with Zn2+, trigger rearrangements of water that extend up to 8 Å away from their surfaces. These findings expand the range of interactions previously thought to occur between ions and proteins by suggesting that (i) weakly hydrated anions can bind complementarily shaped hydrophobic declivities, and that (ii) ion-induced rearrangements of water within protein concavities can (in contrast with similar rearrangements in bulk water) extend well beyond the first hydration shells of the ions that trigger them. This study paints a picture of Hofmeister anions as a set of structurally varied ligands that differ in size, shape, and affinity for water and, thus, in their ability to bind to--and to alter the hydration structure of--polar, nonpolar, and topographically complex concavities on protein surfaces.
    Journal of the American Chemical Society 03/2015; DOI:10.1021/jacs.5b00187 · 11.44 Impact Factor
  • Jerome M Fox, George M Whitesides
    [Show abstract] [Hide abstract]
    ABSTRACT: Spreading fires are noisy (and potentially chaotic) systems in which transitions in dynamics are notoriously difficult to predict. As flames move through spatially heterogeneous environments, sudden shifts in temperature, wind, or topography can generate combustion instabilities, or trigger self-stabilizing feedback loops, that dramatically amplify the intensities and rates with which fires propagate. Such transitions are rarely captured by predictive models of fire behavior and, thus, complicate efforts in fire suppression. This paper describes a simple, remarkably instructive physical model for examining the eruption of small flames into intense, rapidly moving flames stabilized by feedback between wind and fire (i.e., "wind-fire coupling"-a mechanism of feedback particularly relevant to forest fires), and it presents evidence that characteristic patterns in the dynamics of spreading flames indicate when such transitions are likely to occur. In this model system, flames propagate along strips of nitrocellulose with one of two possible modes of propagation: a slow, structured mode, and a fast, unstructured mode sustained by wind-fire coupling. Experimental examination of patterns in dynamics that emerge near bifurcation points suggests that symptoms of critical slowing down (i.e., the slowed recovery of the system from perturbations as it approaches tipping points) warn of impending transitions to the unstructured mode. Findings suggest that slowing responses of spreading flames to sudden changes in environment (e.g., wind, terrain, temperature) may anticipate the onset of intense, feedback-stabilized modes of propagation (e.g., "blowup fires" in forests).
    Proceedings of the National Academy of Sciences 02/2015; DOI:10.1073/pnas.1417043112 · 9.81 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Magnetic levitation (MagLev) enables rapid and non-destructive quality control of plastic parts. The feasibility of MagLev as a method to: i) rapidly assess injection-molded plastic parts for defects during process optimization, ii) monitor the degradation of plastics after exposure to harsh environmental conditions, and iii) detect counterfeit polymers by density is demonstrated. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    Advanced Materials 01/2015; DOI:10.1002/adma.201405207 · 15.41 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: This paper investigates the influence of the interface between a gold or silver metal electrode and an n-alkyl SAM (supported on that electrode) on the rate of charge transport across junctions with structure Met(Au or Ag)TS/A(CH2)nH//Ga2O3 by comparing measurements of current density, J(V), for Met/AR = Au/thiolate (Au/SR), Ag/thiolate (Ag/SR), Ag/carboxylate (Ag/O2C), and Au/acetylene (Au/C≡CR), where R is an n-alkyl group. Values of J0 and β (from the Simmons equation) were indistinguishable for these four interfaces. Since the anchoring groups, A, have large differences in their physical and electronic properties, the observation that they are indistinguishable in their influence on the injection current, J0 (V = 0.5) indicates that these four Met/A interfaces do not contribute to the shape of the tunneling barrier in a way that influences J(V).
    ACS Nano 01/2015; 9(2). DOI:10.1021/nn5059216 · 12.03 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: This paper demonstrates the enrichment of reticulocytes by centrifuging whole blood through aqueous multiphase systems (AMPSs)—immiscible phases of solutions of polymers that form step-gradients in density. The interfaces of an AMPS concentrate cells; this concentration facilitates the extraction of blood enriched for reticulocytes. AMPS enrich reticulocytes from blood from both healthy and hemochromatosis donors. Varying the osmolality and density of the phases of AMPS provides different levels of enrichment and yield of reticulocytes. A maximum enrichment of reticulocytemia of 64 ± 3 % was obtained from donors with hemochromatosis. When used on peripheral blood from normal donors, AMPS can provide a higher yield of enriched reticulocytes and a higher proportion of reticulocytes expressing CD71 than differential centrifugation followed by centrifugation over Percoll. Blood enriched for reticulocytes by AMPS could be useful for research on malaria. Several species of malaria parasites show a preference to invade young erythrocytes and reticulocytes; this preference complicates in vitro cultivation of these species in human blood. Plasmodium knowlesi malaria parasites invade normal human blood enriched for reticulocytes by AMPSs at a rate 2.2 times greater (p-value < 0.01) than they invade unenriched blood. Parasite invasion in normal blood enriched by AMPS was 1.8 times greater (p-value < 0.05) than in blood enriched to a similar reticulocytemia by differential centrifugation followed by centrifugation over Percoll. The enrichment of reticulocytes that are invaded by malaria parasites demonstrates that AMPSs can provide a label-free method to enrich cells for biological research.
    American Journal of Hematology 01/2015; 90(1). DOI:10.1002/ajh.23860 · 3.48 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Soft devices can be bent, stretched, and compressed reversibly, but conventional wires are rigid. This work describes stretchable composites that are easily fabricated with simple tools and commodity materials, and that can provide a strategy for electrical wiring that meets certain needs of soft devices. These composites are made by combining metal wool and elastomeric polymers. Embedding fine (average fiber width ≈25 μm) steel wool (or other metal wools) in a silicone polymer creates an electrically conductive path through the nonconductive elastomer. This composite is flexible, stretchable, compressible, inexpensive, and simple to incorporate into the bodies of soft devices. It is also electrically anisotropic, and shows maximum conductivity along the majority axis of the fibers, but maximum extension perpendicular to this axis. The utility of this composite for creating an electrically conductive path through an elastomer was demonstrated in several devices, including: a soft, solderless breadboard, a soft touch sensor, and a soft strain gauge.
    Advanced Functional Materials 01/2015; DOI:10.1002/adfm.201403396 · 10.44 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Although simple and low-cost interventions for sickle cell disease (SCD) exist in many developing countries, child mortality associated with SCD remains high, in part, because of the lack of access to diagnostic tests for SCD. A density-based test using aqueous multiphase systems (SCD-AMPS) is a candidate for a low-cost, point-of-care diagnostic for SCD. In this paper, the field evaluation of SCD-AMPS in a large (n = 505) case-control study in Zambia is described. Of the two variations of the SCD-AMPS used, the best system (SCD-AMPS-2) demonstrated a sensitivity of 86% (82-90%) and a specificity of 60% (53-67%). Subsequent analysis identified potential sources of false positives that include clotting, variation between batches of SCD-AMPS, and shipping conditions. Importantly, SCD-AMPS-2 was 84% (62-94%) sensitive in detecting SCD in children between 6 months and 1 year old. In addition to an evaluation of performance, an assessment of end-user operability was done with health workers in rural clinics in Zambia. These health workers rated the SCD-AMPS tests to be as simple to use as lateral flow tests for malaria and HIV.
    PLoS ONE 12/2014; 9(12):e114540. DOI:10.1371/journal.pone.0114540 · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: This paper reports the development of Metal-amplified Density Assays, or MADAs - a method of conducting quantitative or multiplexed assays, including immunoassays, by using Magnetic Levitation (MagLev) to measure metal-amplified changes in the density of beads labeled with biomolecules. The binding of target analytes (i.e. proteins, antibodies, antigens) to complementary ligands immobilized on the surface of the beads, followed by a chemical amplification of the binding in a form that results in a change in the density of the beads (achieved by using gold nanoparticle-labeled biomolecules, and electroless deposition of gold or silver), translates analyte binding events into changes in density measureable using MagLev. A minimal model based on diffusion-limited growth of hemispherical nuclei on a surface reproduces the dynamics of the assay. A MADA - when performed with antigens and antibodies - is called a Density-Linked Immunosorbent Assay, or DeLISA. Two immunoassays provided a proof of principle: a competitive quantification of the concentration of neomycin in whole milk, and a multiplexed detection of antibodies against Hepatitis C virus NS3 protein and syphilis T. pallidum p47 protein in serum. MADAs, including DeLISAs, require, besides the requisite biomolecules and amplification reagents, minimal specialized equipment (two permanent magnets, a ruler or a capillary with calibrated length markings) and no electrical power to obtain a quantitative readout of analyte concentration. With further development, the method may be useful in resource-limited or point-of-care settings.
    Lab on a Chip 12/2014; 15(4). DOI:10.1039/c4lc01161a · 5.75 Impact Factor
  • Article: Ionic skin
    [Show abstract] [Hide abstract]
    ABSTRACT: Electronic skins (i.e., stretchable sheets of distributed sensors) report signals using electrons, whereas natural skins report signals using ions. Here, ionic conductors are used to create a new type of sensory sheet, called "ionic skin". Ionic skins are highly stretchable, transparent, and biocompatible. They readily measure strains from 1% to 500%, and pressure as low as 1 kPa.
    Advanced Materials 12/2014; 26(45). DOI:10.1002/adma.201403441 · 15.41 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The hydrophobic effect—the tendency of nonpolar solutes to aggregate in aqueous solution, and the driving force of many biomolecular recognition events—arises from the energetically favorable rearrangement of molecules of water. A detailed understanding of the mechanism by which these rearrangements alter the thermodynamics of ligand-protein interactions is essential for (i) predicting the thermodynamic influence of conditions that alter solvation structure (e.g. the presence of other solutes, structural changes in interacting species) and for (ii) exploiting the hydrophobic effect in the rational design of tight-binding ligands. In this work, we studied the thermodynamic repercussions of incremental perturbations to solvation structure by examining the influence of Hofmeister anions on the thermodynamics of hydrophobic interactions between Human Carbonic Anhydrase II (HCA, EC 4.2.11) and arylsulfonamide ligands. Using a combination of calorimetry, x-ray crystallography, and molecular dynamics simulations, we show that chaotropes displace the zinc-bound water inside the active site of HCAII, triggering rearrangements in networks of water that give rise to large and nearly compensating changes in the enthalpy and entropy of binding. These changes scale with the surface tension increment of these ions and, eventually, give rise to an entropically dominated hydrophobic effect that differs dramatically from the enthalpically dominated effect that governs HCAII-arylsulfonamide association in the absence of Hofmeister anions. We will discuss the implications of these results for existing theories of hydrophobic ligand-protein interactions.
    14 AIChE Annual Meeting; 11/2014
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Diagnostic tests in resource-limited settings require technologies that are affordable and easy to use with minimal infrastructure. Colorimetric detection methods that produce results that are readable by eye, without reliance on specialized and expensive equipment, have great utility in these settings. We report a colorimetric method that integrates a paper-based immunoassay with a rapid, visible-light-induced polymerization to provide high visual contrast between a positive and a negative result. Using Plasmodium falciparum histidine-rich protein 2 as an example, we demonstrate that this method allows visual detection of proteins in complex matrices such as human serum and provides quantitative information regarding analyte levels when combined with cellphone-based imaging. It also allows the user to decouple the capture of analyte from signal amplification and visualization steps.
    Lab on a Chip 11/2014; 15(3). DOI:10.1039/C4LC01239A · 5.75 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: This paper compares rates of charge transport across self-assembled monolayers (SAMs) of n-alkanethiolates having odd and even numbers of carbon atoms (nodd and neven) using junctions with the structure MTS/SAM//Ga2O3/EGaIn (M = Au or Ag). Measurements of current density, J(V), across SAMs of n-alkanethiolates on AuTS and AgTS demonstrated a statistically significant odd-even effect on AuTS, but not on AgTS, that could be detected using this technique. Statistical analysis showed the values of tunneling current density across SAMs of n-alkanethiolates on AuTS with nodd and neven belong to two separate sets, and while there is a significant difference between the values of injection current density, J0, for these two series (log|J0Au,even| = 4.0±0.3 and log|J0Au,odd| = 4.5±0.3), the values of tunneling decay constant, β, for nodd and neven alkyl chains are indistinguishable (βAu,even = 0.73±0.02 Å-1, and βAu,odd= 0.74±0.02 Å-1). A comparison of electrical characteristics across junctions of n-alkanethiolate SAMs on gold and silver electrodes yields indistinguishable values of β and J0, and indicates that a change that substantially alters the tilt angle of the alkyl chain (and, therefore, the thickness of the SAM) has no influence on the injection current density across SAMs of n-alkanethiolates.
    Journal of the American Chemical Society 11/2014; DOI:10.1021/ja509436k · 11.44 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: doi: 10.1021/ac5020782
    Analytical Chemistry 11/2014; DOI:10.1021/ac5020782 · 5.83 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Optical metasurfaces-patterned arrays of plasmonic nanoantennas that enable the precise manipulation of light-matter interactions-are emerging as critical components in many nanophotonic materials, including planar metamaterials, chemical and biological sensors, and photovoltaics. The development of these materials has been slowed by the difficulty of efficiently fabricating patterns with the required combinations of intricate nanoscale structure, high areal density, and/or heterogeneous composition. One convenient strategy that enables parallel fabrication of periodic nanopatterns uses self-assembled colloidal monolayers as shadow masks; this method has, however, not been extended beyond a small set of simple patterns and, thus, has remained incompatible with the broad design requirements of metasurfaces. This paper demonstrates a technique-shadow-sphere lithography (SSL)-that uses sequential deposition from multiple angles through plasma-etched microspheres to expand the variety and complexity of structures accessible by colloidal masks. SSL harnesses the entire, relatively unexplored, space of shadow-derived shapes and-with custom software to guide multiangled deposition-contains sufficient degrees of freedom to (i) design and fabricate a wide variety of metasurfaces that incorporate complex structures with small feature sizes and multiple materials and (ii) generate, in parallel, thousands of variations of structures for high-throughput screening of new patterns that may yield unexpected optical spectra. This generalized approach to engineering shadows of spheres provides a new strategy for efficient prototyping and discovery of periodic metasurfaces.
    ACS Nano 09/2014; DOI:10.1021/nn504214b · 12.03 Impact Factor

Publication Stats

62k Citations
6,398.90 Total Impact Points


  • 1984–2015
    • Harvard University
      • • Department of Chemistry and Chemical Biology
      • • School of Engineering and Applied Sciences
      • • Area of Applied Physics
      Cambridge, Massachusetts, United States
  • 2014
    • Technische Universität München
      München, Bavaria, Germany
  • 2013
    • Boston Children's Hospital
      Boston, Massachusetts, United States
  • 2010
    • Washington University in St. Louis
      • Department of Energy, Environmental, and Chemical Engineering
      Saint Louis, MO, United States
    • University of Alicante
      Alicante, Valencia, Spain
  • 2007
    • University of Wisconsin, Madison
      • Department of Biochemistry
      Madison, MS, United States
  • 2002–2004
    • California Institute of Technology
      • Gates and Crellin Laboratories of Chemistry
      Pasadena, California, United States
    • Cornell University
      Итак, New York, United States
    • Harvard Medical School
      Boston, Massachusetts, United States
  • 2003
    • Boston University
      • Department of Biochemistry
      Boston, Massachusetts, United States
  • 1966–2002
    • Massachusetts Institute of Technology
      • • Department of Materials Science and Engineering
      • • Department of Chemistry
      Cambridge, Massachusetts, United States
  • 1995
    • University of Pennsylvania
      • Department of Chemistry
      Philadelphia, PA, United States
  • 1985
    • Idenix Pharmaceuticals, Inc.
      Cambridge, Massachusetts, United States