Progress toward multiplexed sample-to-result detection in low resource settings using microfluidic immunoassay cards

In many low resource settings multiple diseases are endemic. There is a need for appropriate multi-analyte diagnostics capable of differentiating between diseases that cause similar clinical symptoms. The work presented here was part of a larger effort to develop a microfluidic point-of-care system, the DxBox, for sample-to-result differential diagnosis of infections that present with high rapid-onset fever. Here we describe a platform that detects disease-specific antigens and IgM antibodies. The disposable microfluidic cards are based on a flow-through membrane immunoassay carried out on porous nitrocellulose, which provides rapid diffusion for short assay times and a high surface area for visual detection of colored assay spots. Fluid motion and on-card valves were driven by a pneumatic system and we present designs for using pneumatic control to carry out assay functions. Pneumatic actuation, while having the potential advantage of inexpensive and robust hardware, introduced bubbles that interfered with fluidic control and affected assay results. The cards performed all sample preparation steps including plasma filtration from whole blood, sample and reagent aliquoting for the two parallel assays, sample dilution, and IgG removal for the IgM assays. We demonstrated the system for detection of the malarial pfHRPII antigen (spiked) and IgM antibodies to Salmonella Typhi LPS (patient plasma samples). All reagents were stored on card in dry form; only the sample and buffer were required to run the tests. Here we detail the development of this platform and discuss its strengths and weaknesses.     

A three-state effective Hamiltonian for symmetric cationic diarylmethanes

We analyze the low-energy electronic structure of a series of symmetric cationic diarylmethanes, which are bridge-substituted derivatives of Michler's Hydrol Blue. We use a four-electron, three-orbital complete active space self-consistent field and multi-state multi-reference perturbation theory model to calculate a three-state diabatic effective Hamiltonian for each dye in the series. We exploit an isolobal analogy between the active spaces of the self-consistent field solutions for each dye to represent the electronic structure in a set of analogous diabatic states. The diabatic states can be identified with the bonding structures in classical resonance-theoretic models of cyanine dyes. We identify diabatic states with opposing charge and bond-order localization, analogous to the classical resonance structures, and a third state with charge on the bridge. While the left- and right-charged structures are similar for all dyes, the structure of the bridge-charged diabatic state, and the Hamiltonian matrix elements connected to it, change significantly across the series. The change is correlated with an inversion of the sign of the charge carrier on the bridge, which changes from an electron pair to a hole as the series is traversed.     

Anomalous excitation spectra of frustrated quantum antiferromagnets

We use series expansions to study the excitation spectra of spin-1/2 antiferromagnets on anisotropic triangular lattices. For the isotropic triangular lattice model (TLM), the high-energy spectra show several anomalous features that differ strongly from linear spin-wave theory (LSWT). Even in the Néel phase, the deviations from LSWT increase sharply with frustration, leading to rotonlike minima at special wave vectors. We argue that these results can be interpreted naturally in a spinon language and provide an explanation for the previously observed anomalous finite-temperature properties of the TLM. In the coupled-chains limit, quantum renormalizations strongly enhance the one-dimensionality of the spectra, in agreement with experiments on Cs2CuCl4.     

Harmonic entanglement with second-order nonlinearity

We investigate the second-order nonlinear interaction as a means to generate entanglement between fields of differing wavelengths and show that perfect entanglement can, in principle, be produced between the fundamental and second-harmonic fields in these processes. Neither pure second-harmonic generation nor parametric oscillation optimally produce entanglement; such optimal entanglement is rather produced by an intermediate process.     

Definability in substructure orderings, III: Finite distributive lattices

Let ${{\mathcal D}}$ be the ordered set of isomorphism types of finite distributive lattices, where the ordering is by embeddability. We study first-order definability in this ordered set. We prove among other things that for every finite distributive lattice D, the set {d, d ^opp} is definable, where d and d ^opp are the isomorphism types of D and its opposite (D turned upside down). We prove that the only non-identity automorphism of ${{\mathcal D}}$ is the opposite map. Then we apply these results to investigate definability in the closely related lattice of universal classes of distributive lattices. We prove that this lattice has only one non-identity automorphism, the opposite map; that the set of finitely generated and also the set of finitely axiomatizable universal classes are definable subsets of the lattice; and that for each element K of the two subsets, {K, K ^opp} is a definable subset of the lattice.     

NO Reactions Inside Crystals

Reactions of chemisorbed reagents inside the crystalline molecular solid state are rare but offer unexploited methods for selective solvent-free chemical synthesis. Here we show that the greenhouse gas precursor, nitric oxide (NO) is chemisorbed by crystals of the hexafluorophosphate salts of complexes containing dicobalt sites. On NO sorption a cascade of reactions results in the in-crystal synthesis of nitrite and other gaseous NO_x. Recrystallization enabled structural elucidation of the mixed valent {[(bpbp)Co₂(μ-(η¹-O : η¹-N)-ONO)]₂(bdc)}⁴⁺ (bpbp=2,6-bis(N,N-bis(2-pyridylmethyl)aminomethyl)-4-tert-butylphenolato, bdc=1,4-benzenedicarboxylato) cation. Overlapping signals in the solid-state EPR spectra confirm the Co^IICo^III oxidation state and the presence of NO₂ trapped inside the unrecrystallised solid products (br. g=4, triplet g=2 (340 mT), A(N)=73 MHz), despite three cycles of vacuum and N₂ flushing. Consistently, ν_N−O bands appear in the Raman and IR spectra that are due to the coordinated nitrate and the trapped NO₂ that were synthesized in-crystal. The latter is expelled by heating the solid to 160 °C or by recrystallization. Dimetallic cooperativity is proposed for the NO transformations in these rare examples of selective, chemisorptive substrate reactions in the solid-state.