CONTENTSshould be inexpensive disposable chips or cartridges that include microfluidic features to provide or control sample preparation, flow rate, mixing with reagents, reaction time associated with binding events, filtration of nonanalytical components of the sample, separation of interfering agents and of multiple analytes, and an effective measurement capability. 4 POC diagnostics have been extensively reviewed in recent years, from the points of view of both use 5 and development. 6 The reviews have included coverage of micrototal analysis systems (μTAS), 7 miniaturized isothermal nucleic acid amplification 8 and molecular biological techniques for gene assay, 9 current and anticipated technology for POC infection diagnosis, 10 and microfluidic-based systems leading toward point-of-care detection of nucleic acids and proteins, 11 including multiplexing and labelfree methods. 12 Developments in this area include not only technology but also reliable measurement targets, which in some important areas remain elusive: progress toward viable point-ofcare protein biomarker measurements for cancer detection and diagnostics has been reviewed. 13 We review here the present status of POC diagnostics, emphasizing in particular the past 4 years, then extrapolate their progress into the future. Included are IVD tests for biochemical targets of all sorts relevant to human health, diagnosis, and therapy, as enumerated above. We begin with an overview of the different classes of bioanalytical targets. Then, after setting the context using the well-established glucose and pregnancy POC tests, recent progress in key enabling technologies is reviewed, including traditional and advanced lateral flow approaches, printing and laminating technologies, a range of microfluidic advances, progress in surface chemistry and the control of nonspecificbinding, and developments in labeled and label-free detection approaches. A number of specific innovative examples, in both commercial products and academic POC research, are presented, including assays based on binding to proteins, nucleic acids, and aptamers, with separate sections devoted to blood chemistry, coagulation, and whole cells. We close with trends and future perspectives.Why POC Diagnostics? Time POC measurements provide results rapidly, where needed, and often with major time savings: samples do not travel to a laboratory to await the attention of a skilled technician; results do not wait to be transmitted and collected. Rather, the doctor, nurse, care-giver, patient, or consumer initiates the test and receives the results on the spot. Inevitably this saves time, but speed must not be traded for accuracy or reliability. Figure 1. Idealized POC device. Adapted with permission from ref 6a.

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Stainless steels are used in countless diverse applications for their corrosion resistance. Although they have extremely good general resistance, they are nevertheless susceptible to pitting corrosion. This localized dissolution of an oxide-covered metal in specific aggressive environments is one of the most common and catastrophic causes of failure of metallic structures. The pitting process has been described as random, sporadic and stochastic and the prediction of the time and location of events remains extremely difficult. Many contested models of pitting corrosion exist, but one undisputed aspect is that manganese sulphide inclusions play a critical role. Indeed, the vast majority of pitting events are found to occur at, or adjacent to, such second-phase particles. Chemical changes in and around sulphide inclusions have been postulated as a mechanism for pit initiation but such variations have never been measured. Here we use nanometre-scale secondary ion mass spectroscopy to demonstrate a significant reduction in the Cr:Fe ratio of the steel matrix around MnS particles. These chromium-depleted zones are susceptible to high-rate dissolution that 'triggers' pitting. The implications of these results are that materials processing conditions control the likelihood of corrosion failures, and these data provide a basis for optimizing such conditions.

Diffuse reflectance spectra of 15 mineral species commonly associated with sulphide-bearing mine wastes show diagnostic absorption bands related to electronic processes involving ferric and/or ferrous iron, and to vibrational processes involving water and hydroxyl. Many of these absorption bands are relatively broad and overlapping; however, spectral analysis methods, including continuum removal and derivative analysis, permit most of the minerals to be distinguished. Key spectral differences between the minerals are illustrated in a series of plots showing major absorption band centres and other spectral feature positions. Because secondary iron minerals are sensitive indicators of pH, Eh, relative humidity, and other environmental conditions, spectral mapping of mineral distributions promises to have important application to mine waste remediation studies.

Interfacial adsorption of a mouse monoclonal antibody (type IgG1, anti-beta-hCG) at the hydrophilic silicon oxide/water interface has been studied by spectroscopic ellipsometry and neutron reflection, followed by assessment of binding of a hormonal antigen, human chorionic gonadotrophin (hCG), onto the adsorbed antibody molecules. The amount of adsorption reached a maximum around the isoelectric pH (IP) of 6 for the antibody; this pH-dependent pattern could be altered by increasing salt concentration, a trend also observed for other proteins. Neutron reflection revealed the formation of a 40 A uniform layer from the adsorbed antibody, indicating a flat-on orientation. The subsequent hCG binding showed that the molar ratio of hCG bound to antibody at the interface was as high as 0.7 at low surface coverage of antibody and decreased with increasing surface antibody concentration. The results point to an increasing extent of steric hindrance to hCG access with increasing packing density of antibody molecules on the surface. Comparison with previously published crystal structure studies suggests twisting of the variable region to allow access of the antigen. The binding of hCG was also found to be pH-dependent with its maximum around the IP, if the ionic strength of the solution was low (20 mM). However, if the ionic strength was increased to 200 mM, then hCG binding was influenced by a combination of steric hindrance and electrostatic interaction between the antigen and the surface. These results are highly relevant to the improvement of the performance of biotechnologies such as fertility test pads and biosensors based on antibody immobilization.