Blood contains a range of protein biomarkers that could be used in the early detection of disease. To achieve this, however, requires sensors capable of detecting (with high reproducibility) biomarkers at concentrations one million times lower than the concentration of the other blood proteins. Here, we show that a sandwich assay that combines mechanical and optoplasmonic transduction can detect cancer biomarkers in serum at ultralow concentrations. A biomarker is first recognized by a surface-anchored antibody and then by an antibody in solution that identifies a free region of the captured biomarker. This second antibody is tethered to a gold nanoparticle that acts as a mass and plasmonic label; the two signatures are detected by means of a silicon cantilever that serves as a mechanical resonator for 'weighing' the mass of the captured nanoparticles and as an optical cavity that boosts the plasmonic signal from the nanoparticles. The capabilities of the approach are illustrated with two cancer biomarkers: the carcinoembryonic antigen and the prostate specific antigen, which are currently in clinical use for the diagnosis, monitoring and prognosis of colon and prostate cancer, respectively. A detection limit of 1 × 10(-16) g ml(-1) in serum is achieved with both biomarkers, which is at least seven orders of magnitude lower than that achieved in routine clinical practice. Moreover, the rate of false positives and false negatives at this concentration is extremely low, ∼10(-4).

Ellipsometry was used to investigate the influence of ionic strength (I) and pH on the adsorption of bovine serum albumin (BSA) or beta-lactoglobulin (BLG) onto preabsorbed layers of two polycations: poly(diallyldimethylammonium chloride) (PDADMAC) or poly(4-vinylpyridine bromide) quaternized with linear aliphatic chains of two (QPVP-C2) or five (QPVP-C5) carbons. Comparisons among results for the three polycations reveal hydrophobic interactions, while comparisons between BSA and BLG-proteins of very similar isoelectric points (pI)-indicate the importance of protein charge anisotropy. At pH close to pI, the ionic strength dependence of the adsorbed amount of protein (Gamma) displayed maxima in the range 10 < I < 25 mM corresponding to Debye lengths close to the protein radii. Visualization of protein charge by Delphi suggested that these ionic strength conditions corresponded to suppression of long-range repulsion between polycations and protein positive domains, without diminution of short-range attraction between polycation segments and locally negative protein domains, in a manner similar to the behavior of PE-protein complexes in solution. (1-4) This description was consistent with the disappearance of the maxima at pH either above or below pI. In the former case, Gamma values decrease exponentially with I(1/2), due to screening of attractions, while in the latter case adsorption of both proteins decreased at low I due to strong repulsion. Close to or below pI both proteins adsorbed more strongly onto QPVP-C5 than onto QPVP-C2 or PDADMAC due to hydrophobic interactions with the longer alkyl group. Above pI, the adsorption was more pronounced with PDADMAC because these chains may assume more loosely bound layers due to lower linear charge density.

No abstract

With the urbanisation of the population in developing countries and the process of globalisation, Chagas has become an emerging disease in the urban areas of endemic and non-endemic countries. In 2006, it was estimated that the prevalence of Chagas disease among the general Bolivian population was 6.8%. The aim of the present study was to determine the prevalence of Trypanosoma cruzi infection among Bolivian immigrants living in São Paulo, Brazil. This study had a sample of 633 volunteers who were randomly selected from the clientele of primary care units located in the central districts of São Paulo, Brazil. Infection was detected by two different ELISA assays with epimastigote antigens, followed by an immunoblot with trypomastigote antigens as a confirmatory test. The prevalence of the infection was 4.4%. Risk factors independently associated with the infection were: a history of rural jobs in Bolivia, knowledge of the vector involved in transmission, and having relatives with Chagas disease. Brazil has successfully eliminated household vector transmission of T. cruzi, as well as its transmission by blood transfusion. The arrival of infected immigrants represents an additional challenge to primary care clinics to manage chronic Chagas disease, its vertical transmission, and the blood derivatives and organ transplant programs.