Samuel W. Thomas

Simple Telemedicine for Developing Regions: Camera Phones and Paper-Based Microfluidic Devices for Real-Time, Off-Site Diagnosis

This article describes a prototype system for quantifying bioassays and for exchanging the results of the assays digitally with physicians located off-site. The system uses paper-based microfluidic devices for running multiple assays simultaneously, camera phones or portable scanners for digitizing the intensity of color associated with each colorimetric assay, and established communications infrastructure for transferring the digital information from the assay site to an off-site laboratory for analysis by a trained medical professional; the diagnosis then can be returned directly to the healthcare provider in the field. The microfluidic devices were fabricated in paper using photolithography and were functionalized with reagents for colorimetric assays. The results of the assays were quantified by comparing the intensities of the color developed in each assay with those of calibration curves. An example of this system quantified clinically relevant concentrations of glucose and protein in artificial urine. The combination of patterned paper, a portable method for obtaining digital images, and a method for exchanging results of the assays with off-site diagnosticians offers new opportunities for inexpensive monitoring of health, especially in situations that require physicians to travel to patients (e.g., in the developing world, in emergency management, and during field operations by the military) to obtain diagnostic information that might be obtained more effectively by less valuable personnel.

Mechanism of the hydrophobic effect in the biomolecular recognition of arylsulfonamides by carbonic anhydrase

The hydrophobic effect—a rationalization of the insolubility of nonpolar molecules in water—is centrally important to biomolecular recognition. Despite extensive research devoted to the hydrophobic effect, its molecular mechanisms remain controversial, and there are still no reliably predictive models for its role in protein–ligand binding. Here we describe a particularly well-defined system of protein and ligands—carbonic anhydrase and a series of structurally homologous heterocyclic aromatic sulfonamides—that we use to characterize hydrophobic interactions thermodynamically and structurally. In binding to this structurally rigid protein, a set of ligands (also defined to be structurally rigid) shows the expected gain in binding free energy as hydrophobic surface area is added. Isothermal titration calorimetry demonstrates that enthalpy determines these increases in binding affinity, and that changes in the heat capacity of binding are negative. X-ray crystallography and molecular dynamics simulations are compatible with the proposal that the differences in binding between the homologous ligands stem from changes in the number and organization of water molecules localized in the active site in the bound complexes, rather than (or perhaps in addition to) release of structured water from the apposed hydrophobic surfaces. These results support the hypothesis that structured water molecules—including both the molecules of water displaced by the ligands and those reorganized upon ligand binding—determine the thermodynamics of binding of these ligands at the active site of the protein. Hydrophobic effects in various contexts have different structural and thermodynamic origins, although all may be manifestations of the differences in characteristics of bulk water and water close to hydrophobic surfaces.

Amplifying fluorescent polymer sensors for the explosives taggant 2,3-dimethyl-2,3-dinitrobutane (DMNB).

Structural and electronic effects on the efficiency of DMNB detection with fluorescent conjugated polymers are described.

Towards chemosensing phosphorescent conjugated polymers: cyclometalated platinum(II) poly(phenylene)s

The synthesis and optical properties of several phosphorescent conjugated poly(phenylene)s containing cyclometalated square-planar platinum (II) complexes are reported. These electronic polymers were synthesized via Suzuki cross-coupling of a dibromophenylpyridine-ligated Pt(II) complex with a fluorene diboronic ester. Their optical properties are characterized by relatively strong orange room-temperature phosphorescence with well-resolved vibronic structure in both frozen 2-methyltetrahydrofuran glass and room-temperature fluid solution. Time-resolved phosphorescence spectroscopy has shown that the polymers have excited state lifetimes of approximately 14 μs. These optical properties of the oligomers and polymers are contrasted with those of small model complexes, the optical properties of which have a strong dependence on the identity of the β-diketonate ligand used. The potential utility of phosphorescent conjugated polymers is illustrated by examination of the diffusive quenching due to oxygen as a function of molecular structure.

Twisting and piezochromism of phenylene-ethynylenes with aromatic interactions between side chains and main chains

This paper describes a series of three-ring phenylene-ethynylenes (PEs) in which specific, non-covalent arene–arene interactions control conformation in the solid-state. As determined by single crystal X-ray structures, edge-face interactions between benzyl ester side chains and conjugated main chains are observed. In contrast, perfluorobenzyl ester side chains interact cofacially with main chains, resulting in ∼60° torsional angles between neighboring aryl rings in crystalline PEs. Absorbance and fluorescence spectra of films of these compounds reflect these conformational effects, with the spectra of perfluorobenzyl-substituted compounds shifting hypsochromically from solution- to solid-state. In a demonstration of how balancing non-covalent interactions can open the way to new responsive materials, a main chain twisted derivative with octyloxy substituents displayed significant piezochromic behavior.

Patterns of Electrostatic Charge and Discharge in Contact Electrification

Here we describe a study of the charging and discharging of solids in a system comprising a metal sphere that rolls across an electrically insulating plate. There are two kinetically distinct processes: 1) charging at a constant rate; 2) abrupt discharging, when the potential difference between sphere and surface reaches a critical value determined by the dielectric strength of air. This work has two objectives: 1) to develop a procedure for examining the rate of charging and discharging as a function of a range of relevant variables; 2) to use this information to test the hypotheses that charge separation involved ions and that discharge of the potential produced involved a breakdown of air. In published work, we have described this system; this study demonstrates the wealth of quantitative information it can provide as a tool for studying the atomic/molecular mechanisms of contact electrification. These mechanisms are relevant to processes ranging from lightning to xerography, and are a subject of active controversy. Three mechanisms appear to contribute to contact electrification: 1) ion transfer between surfaces having mobile ions, 2) partitioning of ions from adsorbed water onto the surfaces of non-ionic insulators, and 3) electron transfer between conductors and semiconductors (materials with mobile electrons and well-defined Fermi surfaces). We have concluded—in agreement with a hypothesis by Diaz —that the transfer of ions between the contacting surfaces is the most common mechanism for charge separation when organic materials are involved. The data we present here are consistent with contact charging by the slow transfer of ions, interrupted by episodic, rapid discharge events involving ionized plasmas when the difference in electrical potential between the surfaces exceeds the breakdown limit of air. These experiments used the rolling sphere tool (RST, Figure 1) developed by Grzybowski et al. We investigated contact electrification between stainless steel spheres (d= 3.2 mm) and three different surfaces (relative humidity, RH = 20–25 %, T 22 8C, w = 80 rpm). The Supporting Information contains the experimental procedures we followed for preparing the insulating surfaces: 1) glass (a 1.0 mm thick, 76 mm diameter wafer of low-alkali glass); 2) glass silanized with N-trimethoxysilylpropyl-N,N,N-trimethylammonium chloride; 3) glass silanized with 3-(trihydroxysilyl)-1-propane-sulfonic acid. When the sphere was far (more than ca. 2.5 cm) from the electrode (width 5 mm, 0.2 radians), the electrometer reported only the charge on the portion of the insulator (the glass plate) to which the electrode coupled (Qw). When the sphere passed over the electrode, the electrometer registered a peak in the charge, the height of which was the sum (Qs+w) of the charges that the electrode sensed on the sphere (Qs) and Qw. Figure 2a shows the charge the electrometer recorded for one revolution of the sphere. The fullwidth at half-maximum of the peak was about 0.63 radians. Figure 2b shows a representative plot of the complex pattern of charge (Q, in picocoulomb, pC: 1 pC = 6.2 ; 10 elementary charges) the electrometer reported as the sphere rolled on a glass wafer. When the sphere was directly over the electrode, the electrometer measured a fraction of the charge on the sphere (80–90 %; see the Supporting Information). Qw (grey dot-dash guidelines) and Qs+w (black dashed guidelines) increased linearly with time. Sharp discontinuities— discharge events through air—interrupted the charging. Subtracting Qw from Qs+w gave Qs—the charge that the electrometer sensed on the rolling sphere alone—as a function of time (Figure 2c). We have observed qualitatively similar behavior on a variety of materials, including organic polymers; we will detail these experiments in a full paper. The polarity of charge separation was invariant when a steel sphere (positive) rolled on a clean glass wafer (negative) (Figure 3a). When the sphere rolled on a surface with bound Figure 1. Illustration of the “rolling sphere tool” to measure the kinetics of contact electrification between rolling stainless steel spheres and insulating surfaces. The Supporting Information contains additional graphical representations.

Controlling Contact Electrification with Photochromic Polymers

Contact electrification, the separation of charge when contacting materials separate, is important in a number of applications including electrophotography and the beneficiation of coal. Contact electrification also causes adhesion of particles that inhibit the performance of equipment, or discharges that ignite flammable vapors. Controlling contact electrification, however, remains an unsolved problem. Chemical approaches to controlling contact electrification include aggressive treatments like plasma or mineral acids to chemically modify the surface in a largely undefined manner, additives such as charge-control agents, or covalently modifying surfaces with groups that bear “mobile” ions that are not covalently bound (ionic electrets). Whether the mechanism of insulator contact electrification involves the transfer of ions, 9] electrons, or a combination thereof 11] is a matter of debate; a correlation appears to exist, however, between the hydrophobicity of materials that are not ionic electrets and their charging. Photochromic molecules transition reversibly between chemical structures upon absorption of light, often with substantially different degrees of hydrophobicity. Their applications (among many) include color-changing eyewear, fluorescence imaging, and molecular logic. Herein we describe spiropyran-based photochromic polymers that reversibly change contact electrification behavior upon irradiation. We used a previously described instrument to measure the dynamics of contact electrification. Briefly, a magnetic stir plate causes a ferromagnetic steel sphere to roll in a circular path on an electrically insulating film. Our experiments interrogate the effect of the chemical structure of the insulating film on contact electrification of the rolling sphere. With each revolution of the sphere, it passes over an electrode (connected to an electrometer) that measures charge on the sphere. When the sphere is far from the electrode, it measures only the charge on the dielectric close to the electrode. Because the sphere passes over the electrode repeatedly, we can determine the rate of contact electrification. We performed studies in a Faraday cage to mitigate artifacts from external electric fields, at 20–25 % relative humidity (RH) and 20–22 8C. We prepared the nitrospiropyran-containing methacrylic monomer SPMA in four steps using modified literature procedures. Photochromic spiropyrans reversibly form zwitterionic merocyanines (MC) upon UV irradiation (Scheme 1a). As summarized in Scheme 1b, we prepared

Infochemistry and infofuses for the chemical storage and transmission of coded information

This article describes a self-powered system that uses chemical reactions—the thermal excitation of alkali metals—to transmit coded alphanumeric information. The transmitter (an “infofuse”) is a strip of the flammable polymer nitrocellulose patterned with alkali metal ions; this pattern encodes the information. The wavelengths of 2 consecutive pulses of light represent each alphanumeric character. While burning, infofuses transmit a sequence of pulses (at 5–20 Hz) of atomic emission that correspond to the sequence of metallic salts (and therefore to the encoded information). This system combines information technology and chemical reactions into a new area—“infochemistry”—that is the first step toward systems that combine sensing and transduction of chemical signals with multicolor transmission of alphanumeric information.

A Non-Chromatographic Method for the Purification of a Bivalently Active Monoclonal IgG Antibody from Biological Fluids

This paper describes a method for the purification of monoclonal antibodies (rat anti-2,4-dinitrophenyl IgG: IgG(DNP); and mouse antidigoxin IgG: IgG(Dgn)) from ascites fluid. This procedure (for IgG(DNP)) has three steps: (i) precipitation of proteins heavier than immunoglobulins with ammonium sulfate; (ii) formation of cyclic complexes of IgG(DNP) by causing it to bind to synthetic multivalent haptens containing multiple DNP groups; (iii) selective precipitation of these dimers, trimers, and higher oligomers of the target antibody, followed by regeneration of the free antibody. This procedure separates the targeted antibody from a mixture of antibodies, as well as from other proteins and globulins in a biological fluid. This method is applicable to antibodies with a wide range of monovalent binding constants (0.1 microM to 0.1 nM). The multivalent ligands we used (derivatives of DNP and digoxin) isolated IgG(DNP) and IgG(Dgn) from ascites fluid in yields of >80% and with >95% purity. This technique has two advantages over conventional chromatographic methods for purifying antibodies: (i) it is selective for antibodies with two active Fab binding sites (both sites are required to form the cyclic complexes) over antibodies with one or zero active Fab binding sites; (ii) it does not require chromatographic separation. It has the disadvantage that the structure of the hapten must be compatible with the synthesis of bi- and/or trivalent analogues.

Electronic Effects of Ring Fusion and Alkyne Substitution on Acene Properties and Reactivity

This paper describes the synthesis and systematic study of substituted acenes that have differences in conjugation both along their long axes (by the number of fused benzene or thiophene rings) and along their short axes (by the number of arylethynyl substituents). These acenes include what we believe to be the first reported examples of five new subclasses of substituted acenes. Systematic analyses of data obtained using absorbance and fluorescence spectroscopies, cyclic voltammetry, and DFT calculations reveal clear correlations between these common structural perturbations to acene structure and the key parameters, such as HOMO-LUMO gap, frontier molecular orbital energies, and reactivity with singlet oxygen.