Managing Heart Failure at Home With Point-of-Care Diagnostics.

The objective of this paper is development of an inexpensive point-of-care sensor for detecting the primary heart failure marker peptide, NT-proBNP. The device technology is based on an antibody sandwich assay, but with three innovative aspects. First, chemical amplification is carried out via oxidation of silver nanoparticles (NPs) attached to signaling antibodies rather than by enzymatic amplification. The electrochemical method is faster and eliminates the need for long-term storage of enzymes. Second, the antibody sandwich is formed on mobile magnetic beads. This enhances the rate of mass transfer of the biomarker and the signaling antibody to the primary detection antibody, which is immobilized on the magnetic beads. Third, the sensor itself is fabricated on a paper platform with screen-printed electrodes. This coupled with assembly by simple paper folding, keeps the cost of the sensor low. Here, we report on two separate assays. The first is based on a simple biotin-streptavidin conjugate, which is a preliminary model for the antibody assay. The results indicate a detection limit of 2.1 pM of silver NPs and an assay time of 7 min. The actual NT-proBNP antibody assay takes somewhat longer, and the dynamic detection range is higher: 2.9-582 nM. On the basis of the results presented in this paper, we conclude that this inexpensive paper-based sensor represents a viable technology for point-of-care testing of NT-proBNP, but nevertheless several challenges remain prior to clinical implementation. These include attaining a lower detection limit and better reproducibility, and optimizing the device for human blood.

New Functionalities for Paper-Based Sensors Lead to Simplified User Operation, Lower Limits of Detection, and New Applications.

In the last decade, paper analytical devices (PADs) have evolved into sophisticated yet simple sensors with biological and environmental applications in the developed and developing world. The focus of this review is the technological improvements that have over the past five years increased the applicability of PADs to real-world problems. Specifically, this review reports on advances in sample processing, fluid flow control, signal amplification, and component integration. Throughout, we have sought to emphasize advances that retain the main virtues of PADs: low cost, portability, and simplicity.

Quantitative electrochemical metalloimmunoassay for TFF3 in urine using a paper analytical device.

We report a paper-based assay platform for the detection of the kidney disease marker Trefoil Factor 3 (TFF3) in human urine. The sensor is based on a quantitative metalloimmunoassay that can determine TFF3 concentrations via electrochemical detection of environmentally stable silver nanoparticle (AgNP) labels attached to magnetic microbeads via a TFF3 immunosandwich. The paper electroanalytical device incorporates two preconcentration steps that make it possible to detect concentrations of TFF3 in human urine at the low end of the target TFF3 concentration range (0.03-7.0 µg mL(-1)). Importantly, the paper device provides a level of accuracy for TFF3 determination in human urine equivalent to that of a commercial kit. The paper sensor has a dynamic range of ∼2.5 orders of magnitude, only requires a simple, one-step incubation protocol, and is fast, requiring only 10 min to complete. The cost of the materials at the prototypic laboratory scale, excluding reagents, is just US$0.42.

Wire, mesh, and fiber electrodes for paper-based electroanalytical devices.

Here, we report the use of microwire and mesh working electrodes in paper analytical devices fabricated by origami paper folding (oPADs). The important new result is that Au wires and carbon fibers having diameters ranging from micrometers to tens of micrometers can be incorporated into oPADs and that their electrochemical characteristics are consistent with the results of finite element simulations. These electrodes are fully compatible with both hollow channels and paper channels filled with cellulose fibers, and they are easier to incorporate than typical screen-printed carbon electrodes. The results also demonstrate that the Au electrodes can be cleaned prior to device fabrication using aggressive treatments and that they can be easily surface modified using standard thiol-based chemistry.

Crowded bis ligand complexes of Ttz(Ph,Me) with first row transition metals rearrange due to ligand field effects: structural and electronic characterization (Ttz(Ph,Me) = tris(3-phenyl-5-methyl-1,2,4-triazolyl)borate).

The tris(3-phenyl-5-methyl-1,2,4-triazolyl)borate (Ttz(Ph,Me)) ligand provides intermediate steric bulk and forms predominantly bis(ligand) complexes of the form M(Ttz(Ph,Me))(2) with first row divalent transition metals (1(M), M = Zn, Cu, Ni, Co, Fe, Mn). Due to ligand field effects that are greatest with Ni and Cu, ligand rearrangement is favored with these metals and Cu(Ttz(Ph,Me)*)(2) (1(Cu)*) and (Ttz(Ph,Me)*)Ni(Ttz(Ph,Me)) (1(Ni)*) were isolated by selective recrystallization and fully characterized (* indicates a rearranged Ttz ligand with Ph and Me in swapped positions in one triazole ring). For comparison with Co(Ttz(Ph,Me))(2), the less bulky analogs (Ttz(H,H))(2)Co (4) and (Ttz(Me,Me))(2)Co (5) were studied by NMR and EPR spectroscopy, and 5 was crystallographically characterized. These complexes allow for a study of how slight changes in structure and electron donor properties (for Ni and Cu), as well as dramatic changes in steric bulk (for Co), influence the physical properties; specifically there are significant changes in the UV-Vis, EPR and NMR spectra. Bis(ligand) complexes predominate with all metals, but (Ttz(Ph,Me))Ni(OH(2))Cl (2) and (Ttz(Ph,Me))ZnBr (3) were also isolated and these show that Ttz(Ph,Me) is coordinatively flexible.