Fully integrated wearable sensor arrays for multiplexed in situ perspiration analysis.

Wearable sensor technologies are essential to the realization of personalized medicine through continuously monitoring an individual's state of health. Sampling human sweat, which is rich in physiological information, could enable non-invasive monitoring. Previously reported sweat-based and other non-invasive biosensors either can only monitor a single analyte at a time or lack on-site signal processing circuitry and sensor calibration mechanisms for accurate analysis of the physiological state. Given the complexity of sweat secretion, simultaneous and multiplexed screening of target biomarkers is critical and requires full system integration to ensure the accuracy of measurements. Here we present a mechanically flexible and fully integrated (that is, no external analysis is needed) sensor array for multiplexed in situ perspiration analysis, which simultaneously and selectively measures sweat metabolites (such as glucose and lactate) and electrolytes (such as sodium and potassium ions), as well as the skin temperature (to calibrate the response of the sensors). Our work bridges the technological gap between signal transduction, conditioning (amplification and filtering), processing and wireless transmission in wearable biosensors by merging plastic-based sensors that interface with the skin with silicon integrated circuits consolidated on a flexible circuit board for complex signal processing. This application could not have been realized using either of these technologies alone owing to their respective inherent limitations. The wearable system is used to measure the detailed sweat profile of human subjects engaged in prolonged indoor and outdoor physical activities, and to make a real-time assessment of the physiological state of the subjects. This platform enables a wide range of personalized diagnostic and physiological monitoring applications.

General Thermal Texturization Process of MoS2 for Efficient Electrocatalytic Hydrogen Evolution Reaction.

Molybdenum disulfide (MoS2) has been widely examined as a catalyst containing no precious metals for the hydrogen evolution reaction (HER); however, these examinations have utilized synthesized MoS2 because the pristine MoS2 mineral is known to be a poor catalyst. The fundamental challenge with pristine MoS2 is the inert HER activity of the predominant (0001) basal surface plane. In order to achieve high HER performance with pristine MoS2, it is essential to activate the basal plane. Here, we report a general thermal process in which the basal plane is texturized to increase the density of HER-active edge sites. This texturization is achieved through a simple thermal annealing procedure in a hydrogen environment, removing sulfur from the MoS2 surface to form edge sites. As a result, the process generates high HER catalytic performance in pristine MoS2 across various morphologies such as the bulk mineral, films composed of micron-scale flakes, and even films of a commercially available spray of nanoflake MoS2. The lowest overpotential (η) observed for these samples was η = 170 mV to obtain 10 mA/cm(2) of HER current density.

Carbon nanotube active-matrix backplanes for mechanically flexible visible light and X-ray imagers.

We report visible light and X-ray imagers on lightweight and mechanically flexible plastic substrates. The process involves solution processing of organic photodetectors on top of an active-matrix backplane consisting of carbon nanotube thin-film transistors. The system takes advantage of the high mobility of nanotube transistors for low operating voltages and efficient light absorption of organic bulk-heterojunctions for high imaging sensitivity. With this highly scalable process scheme, 18 × 18 pixel-array flexible imagers (physical size of 2 cm × 1.5 cm) with high performance are successfully demonstrated. In addition, as the absorption peak of the adopted organic photodiodes covers the green band of the light spectrum, X-ray imaging is readily demonstrated by placing a scintillator film on top of the flexible imagers.

Room temperature multiplexed gas sensing using chemical-sensitive 3.5-nm-thin silicon transistors.

There is great interest in developing a low-power gas sensing technology that can sensitively and selectively quantify the chemical composition of a target atmosphere. Nanomaterials have emerged as extremely promising candidates for this technology due to their inherent low-dimensional nature and high surface-to-volume ratio. Among these, nanoscale silicon is of great interest because pristine silicon is largely inert on its own in the context of gas sensing, unless functionalized with an appropriate gas-sensitive material. We report a chemical-sensitive field-effect transistor (CS-FET) platform based on 3.5-nm-thin silicon channel transistors. Using industry-compatible processing techniques, the conventional electrically active gate stack is replaced by an ultrathin chemical-sensitive layer that is electrically nonconducting and coupled to the 3.5-nm-thin silicon channel. We demonstrate a low-power, sensitive, and selective multiplexed gas sensing technology using this platform by detecting H2S, H2, and NO2 at room temperature for environment, health, and safety in the oil and gas industry, offering significant advantages over existing technology. Moreover, the system described here can be readily integrated with mobile electronics for distributed sensor networks in environmental pollution mapping and personal air-quality monitors.

Serum concentration of Hakata antigen, a member of the ficolins, is linked with inhibition of Aerococcus viridans growth.

BACKGROUND: Hakata antigen (Hakata) is a novel serum glycoprotein that consists of collagen- and fibrinogen-like domains, similar to ficolin/p35. Our research suggested that serum Hakata may be a target of a polysaccharide (PSA) produced by Aerococcus viridans. METHODS: A. viridans was incubated with human plasma and Hakata-depleted plasma to examine Hakata binding and growth inhibition of A. viridans through binding with PSA. RESULTS: When A. viridans was mixed with human acid citrate dextrose-one (ACD-A) plasma, it pulled down Hakata complexed with mannose-binding lectin (MBL)-associated serine proteases 1 and 2 (MASP-1 and MASP-2). This complex had the potential for C4 deposition. Serum Hakata circulates as Hakata-MASPs complex in the blood and is proteolytically active. By mixing A. viridans with human plasma, we prepared a Hakata-depleted plasma, deficient in Hakata-MASPs complex. This plasma failed to inhibit A. viridans growth plasma, but does not inhibit Staphylococcus aureus, Yersinia enterocolitica and Escherichia coli. However, a decrease of growth inhibition of A. viridans in Hakata-depleted plasma could be restored by adding a Hakata-MASPs complex preparation in a dose-dependent manner. On the other hand, the Hakata-MASPs complex exhibited strong binding to A. viridans, but not to S. aureus, Y. enterocolitica and E. coli. CONCLUSIONS: The serum concentration of Hakata is linked with growth inhibition of A. viridans upon binding of Hakata via PSA.

Purification, measurement of concentration, and functional complement assay of human ficolins.

Ficolins constitute a group of lectins involved in innate immunity. L-Ficolin, H-ficolin, and M-ficolin are present in human serum. The human ficolins differ in carbohydrate-binding specificity, but they have in common the ability to recognize the acetyl group. L-Ficolin and H-ficolin are associated with serine proteases termed MASPs (MBL-associated serine proteases) and their truncated proteins, and the complexes (L/H-ficolin-MASP) activate the lectin pathway of complement upon binding to their ligands. Recombinant M-ficolin is also able to form a complex with MASP, resulting in complement activation. L-Ficolin and H-ficolin can be purified as a complex with MASP from serum by utilizing their binding specificities. These ficolin-MASP complexes have an ability to activate C4. Human ficolins are quantified by ELISA using specific antibodies or ligands.

Highly deformable liquid-state heterojunction sensors.

Mechanically deformable devices and sensors enable conformal coverage of electronic systems on curved and soft surfaces. Sensors utilizing liquids confined in soft templates as the sensing component present the ideal platform for such applications, as liquids are inherently more deformable than solids. However, to date, liquid-based devices have been limited to metal lines based on a single-liquid component given the difficulty in the fabrication of liquid-based junctions due to intermixing. Here, we demonstrate a robust platform for the fabrication of liquid-liquid 'heterojunction' devices, presenting an important advancement towards the realization of liquid-state electronic systems. The device architecture and fabrication scheme we present are generic for different sensing liquids, enabling demonstration of sensors responsive to different stimuli. As a proof of concept, we demonstrate temperature, humidity and oxygen sensors by using different ionic liquids, exhibiting high sensitivity with excellent mechanical deformability arising from the inherent property of the liquid phase.

Antibody to the central region of human T-lymphotropic virus type 1 gp46 is associated with the progression of adult T-cell leukemia.

Human T-cell lymphotropic virus type 1 (HTLV-1) is an etiologic agent of adult T-cell leukemia/lymphoma (ATL). HTLV-1 is spread by cell-to-cell transmission via the gp46-197 region, Asp197 to Leu216, on the envelope protein gp46. In the present study, we revealed a positive correlation between the appearance of an antibody recognizing the gp46-197 region (anti-gp46-197 antibody) and the severity of ATL. The prevalence and titer of the anti-gp46-197 antibody were found to be elevated along with the progression of ATL. In serial samples obtained from a single patient, the anti-gp46-197 antibody was detected before treatment in acute phase, then diminished after allogeneic bone marrow transplantation, to which the patient had a complete response. However, the antibody appeared again before a relapse, along with an increase of the serum-soluble interleukin-2 receptor level and proviral load. The results from the other six patients also indicate that seroconversion of this antibody was synchronized with the deterioration of ATL. Taken together, the findings indicate that the anti-gp46-197 antibody may be a novel beacon for gauging the efficacy of therapeutic approaches to ATL, and a survey of this antibody would be useful for identifying asymptomatic carriers infected with HTLV-1 who are at high risk of developing ATL.

Activation of the lectin complement pathway by H-ficolin (Hakata antigen).

Ficolins are a group of proteins which consist of a collagen-like domain and a fibrinogen-like domain. In human serum, there are two types of ficolins named L-ficolin/P35 and H-ficolin (Hakata Ag), both of which have lectin activity. We recently demonstrated that L-ficolin/P35 is associated with mannose-binding lectin (MBL)-associated serine proteases (MASP) 1 and 2 and small MBL-associated protein (sMAP), and that the complex activates the lectin pathway. In this study, we report the characterization of H-ficolin in terms of its ability to activate complement. Western blotting analysis showed the presence of MASP-1, MASP-2, MASP-3, and sMAP in H-ficolin preparations isolated from Cohn Fraction III. The MASPs in the preparations had proteolytic activities against C4, C2, and C3 in the fluid phase. When H-ficolin preparations were bound to anti-H-ficolin Ab which had been coated on ELISA plates, they activated C4, although no C4 activation was noted when anti-MBL and anti-L-ficolin/P35 were used. H-ficolin binds to PSA, a polysaccharide produced by Aerococcus viridans. C4 was activated by H-ficolin preparations bound to PSA which had been coated on ELISA plates. These results indicate that H-ficolin is a second ficolin which is associated with MASPs and sMAP, and which activates the lectin pathway.

Novel biomarker of HTLV-1-associated disease: specific appearance of antibody recognizing the receptor-binding site on HTLV-1 envelope protein.

We previously showed that 71-kDa heat shock cognate protein (HSC70) functions as a cellular receptor for gp46 protein via the gp46-197 region, corresponding to Asp197 to Leu216 of human T-cell lymphotropic virus type 1 (HTLV-1), leading to cell-to-cell transmission of HTLV-1. We found that HSC70 protein was contained in goat serum and casein used as blocking agents in the usual ELISA method. Here, it was demonstrated that HSC70 contamination in the blocking agents causes a false-negative result in the detection of anti-gp46-197 antibody in serum samples from HTLV-1-infected individuals. By using ELISA without the blocking agents, we detected antibodies recognizing the HSC70-binding site of gp46, and the anti-gp46-197 antibody specifically appeared in sera from patients with HTLV-1-associated diseases. The frequency of serum anti-gp46-197 antibody-positive individuals was 98% and 100% among ATLL and HAM/TSP patients, respectively, but only 6% among asymptomatic HTLV-1-infected carriers (ACs). The antibody titer in ATLL and HAM/TSP patients was higher than that in ACs (P < 0.002 for ATLL; P < 0.0001 for HAM/TSP). These findings suggest that appearance of the anti-gp46-197 antibody is a predictive marker for the onset of HTLV-1-associated disease.