With the advent of an increased emphasis on the potential to utilize biomarkers in saliva for systemic diseases, the issue of existing oral disease is an important consideration that could adversely affect the interpretation of diagnostic results obtained from saliva. We addressed the question does a patient’s oral inflammation status confound biomarker levels used in diagnosis of acute myocardial infarction (AMI). The results demonstrated that multiple serum biomarkers and a few salivary biomarkers reflected the cardiac event. Importantly, oral health of the individual had minimal impact on the validity of the serum or salivary biomarker effectiveness.
Nicolaos Christodoulides, Richard De La Garza, Glennon Simmons, Michael McRae, Jorge Wong, Thomas Kosten, Craig Miller, Jeffrey Ebersole, John McDevitt
This manuscript describes programmable Bio-Nano-Chip (p-BNC) approach that serves as miniaturized assay platform designed for the rapid detection and quantitation of multiple analytes in biological fluids along with the specific applications in salivary diagnostics intended for the point of need (PON). Included here are oral fluid-based tests for local periodontal disease, systemic cardiac disease and multiplexed tests for drugs of abuse.
A micromachined fluidic sensor array for the rapid characterization of multiple analytes in solution has been developed. A simple micromachined fluidic structure for this biological and chemical agent detection system has been designed and fabricated, and the system has been tested. Sensing occurs via optical changes to indicator molecules that are attached to polymeric microspheres (beads). A separate charged-coupled- device (CCD) is used for the simultaneous acquisition of the optical data from the selectively arranged beads in micromachined etch cavities. The micromachined bead support structure has been designed to be compatible wit this hybrid optical detection system. The structure consists of four layers: cover glass, micromachined silicon, dry film photoresist, and glass substrate. The bottom three layers are fabricated first, and the beads are selectively placed into micromachined etch cavities. Finally, the cover glass is applied to confine the beads. This structure utilizes a hydrophilic surface of the cover glass to draw a liquid sample into the sensor array without moving components, producing a compact, reliable, and potentially low-cost device. We have initially characterized fluid flow through a complete chip, showing complete filling of the sample chamber in approximately 2 seconds. The test results show that this system may be useful in micro total analysis systems ((mu) - TAS), especially in single-use biomedical applications.
Composite dye/superconductor sensors which can discriminate different wavelengths of light in the visible and near- infrared regions have been fabricated. By lithographically patterning 1500 angstroms thick films of the superconductor YBa2Cu3O7-δ on MgO substrates, arrays of microbridges have been created. A layer of dye dispersed in a polymeric matrix is deposited on top of each bridge to create the wavelength selective light absorbing element. Each meandering path bridge is approximately 20 μm wide and approximately 10 mm long. The device functions in a different manner to traditional semiconductor-based light sensing technologies in which a dye structure serves the role of a filtering agent. Here, the response of the hybrid dye/superconductor element is amplitude at wavelengths strongly absorbed by the dye laser. Such devices represent the initial steps towards a larger structure capable of simultaneously sensing wavelength bands from the visible through to the infrared. In addition to dye sensitization method, another approach to adding wavelength selectivity to detectors is described here in which interference effects in micromachined microbolometers are exploited.
The rational design of small molecules for the selective complexation of analytes has reached a level of sophistication such that there exists a high degree of prediction. An effective strategy for transforming these hosts into sensors involves covalently attaching a fluorophore to the receptor which displays some fluorescence modulation when analyte is bound. Competition methods, such as those used with antibodies, are also amenable to these synthetic receptors, yet there are few examples. In our laboratories, the use of common dyes in competition assays with small molecules has proven very effective. For example, an assay for citrate in beverages and an assay for the secondary messenger IP3 in cells have been developed. Another approach we have explored focuses on multi-analyte sensor arrays with attempt to mimic the mammalian sense of taste. Our system utilizes polymer resin beads with the desired sensors covalently attached. These functionalized microspheres are then immobilized into micromachined wells on a silicon chip thereby creating our taste buds. Exposure of the resin to analyte causes a change in the transmittance of the bead. This change can be fluorescent or colorimetric. Optical interrogation of the microspheres, by illuminating from one side of the wafer and collecting the signal on the other, results in an image. These data streams are collected using a CCD camera which creates red, green and blue (RGB) patterns that are distinct and reproducible for their environments. Analysis of this data can identify and quantify the analytes present.
Steven Savoy, John Lavigne, J. Yoo, John Wright, Marc Rodriguez, Adrian Goodey, Bridget McDoniel, John McDevitt, Eric Anslyn, Jason Shear, Andrew Ellington, Dean Neikirk
A micromachined sensor array has been developed for the rapid characterization of multi-component mixtures in aqueous media. The sensor functions in a manner analogous to that of the mammalian tongue, using an array composed of individually immobilized polystyrene-polyethylene glycol composite microspheres selectively arranged in micromachined etch cavities localized o n silicon wafers. Sensing occurs via colorimetric or fluorometric changes to indicator molecules that are covalently bound to amine termination sites on the polymeric microspheres. The hybrid micromachined structure has been interfaced directly to a charged-coupled-device that is used for the simultaneous acquisition of the optical data from the individually addressable `taste bud' elements. With the miniature sensor array, acquisition of data streams composed of red, green, and blue color patterns distinctive for the analytes in the solution are rapidly acquired. The unique combination of carefully chosen reporter molecules with water permeable microspheres allows for the simultaneous detection and quantification of a variety of analytes. The fabrication of the sensor structures and the initial colorimetric and fluorescent responses for pH, Ca+2, Ce+3, and sugar are reported. Interface to microfluidic components should also be possible, producing a complete sampling/sensing system.
A strategy for increasing the wavelength selectivity and responsivity of hybrid dye/superconductor optical sensors is described. Here, reflective 'mirror layers' deposited on the top surface of YBa2Cu3O7-(delta ) thin film devices are used to enhance the optical performance characteristics of such hybrid sensors. Quantification of the wavelength-selectivity for such detector structures is detailed for both dye/high-Tc superconductor and dye/mirror-layer/high-Tc superconductor systems. Optical response studies of the structures suggest that the inclusion of the mirror layer serves to enhance the wavelength-selectivity of the detector. Consequently, only the on-resonance signals captured by the dye layer are effectively sensed by the superconductor element. Measurements of the spectral response properties of the mirror layer-modified hybrid detectors show that energy transfer between the dye and superconducting elements is not diminished by the presence of this reflective layer.
High temperature superconductors provide enhanced sensitivity capabilities as chemical/biological agent detectors. State-of-the-art advances in ruggedizing superconducting platforms make them much more robust for field applications. In addition, microminiaturization and advances in refrigeration have enabled the systems engineering of portable, durable, survivable, low power requirement devices. This presentation describes a prototype system employing YBCO (yttrium barium copper oxide) superconducting quantum interference devices (SQUIDS) with specific biolayer detection dye coatings. These devices may be deployed as specific stand-off detectors, or potentially reconfigured as point sensors. A library of pattern recognition algorithms provides the reference template for the system. The human-system interface will provide a 'yes/no' agent confirmation for the environment being queried, and associated confidence value. This prototype detection system has great potential for deployment in support of hostage rescue/rapid response teams, DMAT, and urban search and rescue. The preparation and characterization of a new generation of optical sensors fabricated from high-temperature superconductor (HTSC) thin films is reported herein. These new hybrid devices are fashioned using HTSC thin films which are coated with organic dye overlayers. These systems are shown to respond selectively to those wavelengths which are absorbed strongly by the molecular dye. Methods for fabricating the superconductor element and depositing the dye layer are discussed. Moreover, resistivity versus temperature measurements before and after dye deposition are utilized to characterize these hybrid structures. The unique optical response properties of these hybrid sensors are also detailed.
A micromachined silicon Fabry-Perot interferometric sensor is demonstrated as an optical chemical sensor. This sensor is based on the combined nature of the amplifying and tuning characteristics of the Fabry-Perot microcavity structure and the doping effect of polymer films such as Poly(3- dodecylthiophene) (P3DDT) upon exposure to an oxidizer, in this case, iodine. The fabricated Fabry-Perot chemical sensors show reversible sensing behavior with a maximum change in transmitted optical intensity of 60%. Significant improvement of the sensing performance is obtained from the Fabry-Perot microcavity structure compared to a simple planar single membrane structure, which indicates the resonant effect of the Fabry-Perot cavity on the chemical sensor. The measured sensing characteristics suggest that the change in absorptance of P3DDT polymer inside the microcavity plays a major role, while the deflection of a microcavity membrane by the P3DDT polymer-induced surface tension gives tunability of the sensor to maximize the amplification of output response by adjusting the Fabry- Perot microcavity gap spacing.
Electrochemical techniques are exploited to fabricate conductive polymer/high Tc superconductor bilayer structures. SCanning electron microscopy and electrochemical techniques are utilized to characterize the electrodeposition of polypyrrole layers grown onto YBa2Cu3O7-(delta ) films. In such hybrid polymer/superconductor systems, it is found that when the polymer is oxidized to its conductive state, the transition temperatures (Tc) and critical currents (Jc) of the underlying superconductor film are suppressed. Reversible modulation of the values of the transition temperatures of up to 50K are noted for these structures. Upon reduction of the conductive polymer layer back to its non-conductive form, both Tc and Jc are found to return to values close to those acquired for the underivatized YBa2Cu3O7-(delta ) film. Moreover, measurements as a function of temperature of the polymer/superconductor interface resistance show dramatic decrease in this value at Tc. ALso, estimates of superconducting coherence lengths within the organic conductor samples suggest superconducting properties over macroscopically large distances within the organic materials can be expected. Collectively these results are consistent with the first observation of a conductive polymer proximity effect.
The preparation and characterization of a new generation of optical sensors fabricated from high-temperature superconductor (HTSC) thin films is reported herein. These new hybrid devices are fashioned using HTSC thin films which are coated with organic dye overlayers. These systems are shown to respond selectively to those wavelengths which are absorbed strongly by the molecular dye. Methods for fabricating the superconductor element and depositing the dye layer are discussed. Moreover, resistivity versus temperature measurements before and after dye deposition are utilized to characterize these hybrid structures. The unique optical response properties of these hybrid sensors are also detailed.
The preparation of a hybrid conducting polymer/high-temperature superconductor device consisting of a polypyrrole coated YBa2Cu3O7-(delta ) microbridge is reported. Electrochemical techniques are exploited to alter the oxidation state of the polymer and, in doing so, it is found that superconductivity can be modulated in a controllable and reproducible fashion by the polymer layer. Whereas the neutral (insulating) polypyrrole only slightly influences the electrical properties of the underlying YBa2Cu3O7-(delta ) film, the oxidized (conductive) polymer depresses Tc by up to 50 K. The observed reversible shifts in Tc are the largest reported to date. In a similar fashion, the oxidation state of the polymer is found to reversibly modulate the magnitude of Jc, the superconducting critical current. Thus, the operation of a molecular/superconductor switch for controlling superconductivity is demonstrated.
The preparation and characterization of a new generation of hybrid optical sensors fabricated from high-temperature superconductor thin films coated with organic dye overlayers is described herein. These dye-coated superconductor structures respond selectively to those wavelengths of light which are absorbed strongly by the molecular dye. Methods for preparing such optical sensors are details. Scanning electron microscopy, resistivity vs. temperature and optical measurements are exploited to characterize the hybrid devices.
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