Digital microfluidics using soft lithography

Although microfluidic chips have demonstrated basic functionality for single applications, performing varied and complex experiments on a single device is still technically challenging. While many groups have implemented control software to drive the pumps, valves, and electrodes used to manipulate fluids in microfluidic devices, a new level of programmability is needed for end users to orchestrate their own unique experiments on a given device. This paper presents an approach for programmable and scalable control of discrete fluid samples in a polydimethylsiloxane (PDMS) microfluidic system using multiphase flows. An immiscible fluid phase is utilized to separate aqueous samples from one another, and a novel "microfluidic latch" is used to precisely align a sample after it has been transported a long distance through the flow channels. To demonstrate the scalability of the approach, this paper introduces a "general-purpose" microfluidic chip containing a rotary mixer and addressable storage cells. The system is general purpose in that all operations on the chip operate in terms of unit-sized aqueous samples; using the underlying mechanisms for sample transport and storage, additional sensors and actuators can be integrated in a scalable manner. A novel high-level software library allows users to specify experiments in terms of variables (i.e., fluids) and operations (i.e., mixes) without the need for detailed knowledge about the underlying device architecture. This research represents a first step to provide a programmable interface to the microfluidic realm, with the aim of enabling a new level of scalability and flexibility for lab-on-a-chip experiments.     

Impact of environmental conditions on the marine natural product bryostatin 1

Marine Natural Products (MNPs), such as bryostatin 1, are exposed to a range of physical and chemical conditions through the life cycle of the host organism. These include exposure to sunlight, oxidizing and reducing agents, cation binding, and adsorption to reactive metal oxide surfaces. Using Fourier Transform-Ion Cyclotron Resonance (FT-ICR), Matrix Assisted Laser Desorption Ionization Mass Spectrometry (MALDI-MS), UV/Vis absorbance spectroscopy, and molecular modeling, we studied the impact of UV light, TiO2, I2, and reaction with FeCl3 on the structure of bryostatin 1. Our results demonstrate that natural conditions transform bryostatin to a number of structures, including one with a molar mass of 806 Da, which we have previously identified in the sediment collected from the Gulf of Mexico. To date, at least 20 different structures of bryostatin have been reported in the literature. This work suggests that these variations may be products of the chemical environment in which the bryozoa Bugula neritina resides and are not the result of genetic variations within Bugula.     

Muonium atom addition to pyridine and to the pyridinium cation

Muonium atoms are found to add mainly to the N-atom and to the ortho and meta positions in pyridine in almost equal amounts, giving pyridinyl and 2-azacyclohexadienyl radicals and 3-azacyclohexadienyl radicals, respectively (no addition was observed at the para site); on protonation, as in a sample of PyH⁺ BF₄⁻, the reactivity follows the positive charge density, being enhanced for addition to the N(H⁺) position, reduced for the ortho/meta positions, and now conferring a significant yield of the para isomer. These results for genuine reactions of hydrogen atoms are discussed in view of studies of radical formation in these materials, made using EPR spectroscopy, when they are exposed to γ-rays in cryogenic matrices, for which mechanisms involving charge-neutralization of initial radical ions are proposed. Copyright © 2001 John Wiley & Sons, Ltd.     

Quantification in histopathology—Can magnetic particles help?

Every year, more than 270,000 people are diagnosed with cancer in the UK alone; this means that one in three people worldwide contract cancer within their lifetime. Histopathology is the principle method for confirming cancer and directing treatment. In this paper, a novel application of magnetic particles is proposed to help address the problem of subjectivity in histopathology. Preliminary results indicate that magnetic nanoparticles cannot only be used to assist diagnosis through improving quantification but also potentially increase throughput, hence offering a way of dramatically reducing costs within the routine histopathology laboratory.     

A simple model for a two-stage chemical reaction with diffusion

We analyse the evolution of a two-stage chemical reaction betweentwo neighbouring plumes of reactants. Under the assumption thatthe plumes are approximately Gaussian we derive a system ofordinary differential equations for the total amount, the centroidand the variance of each reactant. We compare the solution ofthese equations with full numerical simulation of the reaction.Excellent agreement is obtained, with solution of the near-Gaussianmodel requiring considerably less computational effort thanthe full simulations. Of key importance is the yield of thereaction, and we discuss this feature in particular.     

Scaling studies and time-resolved microwave measurements on arelativistic backward-wave oscillator

A relativistic backward-wave oscillator (BWO) operating at a frequency near 8 GHz has been built. The parameters of the 60-ns electron beam driving this microwave source are varied over the ranges 0.8-1.5 MV and 2-10 kA. Several different annular cathodes for launching the electron beam are tried, varying the outer radius and shape. The axial magnetic field guiding the beam through the BWO is varied between 0.6 and 3 T. The power transfer downstream to an output waveguide is investigated as a function of the shape of the transition from the BWO to the waveguide. The scaling of the output power and frequency with these variations is discussed. Time-resolved measurements of 2-ns-long segments of the microwave output are shown. In observations of the microwave signal, it is found that the frequency shifts as the output power envelope passes through a sharp dip. It is proposed that this shift corresponds to a change in the longitudinal operating mode of the BWO     

In silico modeling of p450 substrates, inhibitors, activators, and inducers

Cytochrome P450 enzymes are the predominant mediators of phase I metabolism of exogenous small molecules. As a result of their extensive role in metabolism of xenobiotics, drug compounds, and endogenous compounds, as well as their wide tissue distribution, significant drug discovery resources are spent to avoid interacting with this class of enzymes. Here we review historical and recent in silico modeling of 7 cytochrome P450 enzymes of particular interest, specifically CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. For each we provide a brief biological background including known inhibitors, substrates, and inducers, as well as details of computational modeling efforts and advances in structural biology. We also provide similar details for 3 nuclear receptors known to regulate gene expression of these enzyme families.     

Gaussian Multiplicative Chaos for Symmetric Isotropic Matrices

Motivated by isotropic fully developed turbulence, we define a theory of symmetric matrix valued isotropic Gaussian multiplicative chaos. Our construction extends the scalar theory developed by J.P. Kahane in 1985.