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Nashville, TN, United States

May A.K.,Vanderbilt University | Brady J.S.,Vanderbilt University | Romano-Keeler J.,Vanderbilt University | Drake W.P.,Vanderbilt University | And 4 more authors.
Chest | Year: 2015

BACKGROUND: Ventilator-associated pneumonia (VAP) remains a common complication in critically ill surgical patients, and its diagnosis remains problematic. Exhaled breath contains aerosolized droplets that reflect the lung microbiota. We hypothesized that exhaled breath condensate fluid (EBCF) in hygroscopic condenser humidifier/heat and moisture exchanger (HCH/HME) filters would contain bacterial DNA that qualitatively and quantitatively correlate with pathogens isolated from quantitative BAL samples obtained for clinical suspicion of pneumonia. METHODS: Forty-eight adult patients who were mechanically ventilated and undergoing quantitative BAL (n = 51) for suspected pneumonia in the surgical ICU were enrolled. Per protocol, patients fulfilling VAP clinical criteria undergo quantitative BAL bacterial culture. Immediately prior to BAL, time-matched HCH/HME filters were collected for study of EBCF by real-time polymerase chain reaction. Additionally, convenience samples of serially collected filters in patients with BAL-diagnosed VAP were analyzed. RESULTS: Forty-nine of 51 time-matched EBCF/BAL fluid samples were fully concordant (concordance > 95% by κ statistic) relative to identified pathogens and strongly correlated with clinical cultures. Regression analysis of quantitative bacterial DNA in paired samples revealed a statistically significant positive correlation (r = 0.85). In a convenience sample, qualitative and quantitative polymerase chain reaction analysis of serial HCH/HME samples for bacterial DNA demonstrated an increase in load that preceded the suspicion of pneumonia. CONCLUSIONS: Bacterial DNA within EBCF demonstrates a high correlation with BAL fluid and clinical cultures. Bacterial DNA within EBCF increases prior to the suspicion of pneumonia. Further study of this novel approach may allow development of a noninvasive tool for the early diagnosis of VAP. © 2015 AMERICAN COLLEGE OF CHEST PHYSICIANS. Source


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 2.29M | Year: 2011

DESCRIPTION (provided by applicant): Molecular interactions form the basis of healthy metabolism as well as the manifestation of disease, and comprise the very foundation of drug treatment. Tools available to study molecular interactions in their nascent environment and physiological concentrations without chemical modification, such as surface immobilization or labeling, are limited. Current label-free technologies cannot perform homogeneous (free solution) measurements of membrane protein target interactions. Membrane proteins, which make up about 1/3 of the human proteome, interact with a wide range of biologically relevant species. A specific class of membrane proteins known as G-protein coupled receptors (GPCR) is of particular interest, as they represent the principle drug target for about 40% of all prescription pharmaceuticals and over half of the top one hundred best selling drugs. Currently, there does not exist a practical label-free means to study GPCR - lead interactions as they proceed in their native environment. Consequently, label-free approaches significantly under-serve a major drug discovery need, and as such, there exists a profound requirement for a label-free technique to support research demands in the all important GPCR and membrane protein fields. Molecular Sensing Inc.'s (MSI) Phase II SBIR proposal entitled, High Throughput, Label-free Molecular Interaction Platform for Membrane Protein Targets, leverages the achievements of our Phase I program and is directed towards producing a robust Back-Scattering Interferometry (BSI) instrument for use in drug research. In addition to refining the platform, under Phase II we will demonstrate the unique strengths and capabilities of BSI to significantly advance progress in the all important area of membrane protein drug research by capitalizing on collaborations with three world-class research environments: The Groves Laboratory at the University of California at Berkeley, the Finn Laboratory of Scripps Research Institute, and the Bornhop Laboratory at Vanderbilt University. The culmination of our Phase II program will result in the creation of a prototype research product, which the company will sell to its early access customers in translational and pharmaceutical research markets. Phase III activities will complete the product development process, making this powerful new tool accessible to laboratories worldwide. As our initial market experience of Phase I technology has taught, our commercial product will create a sustained impact to basic, translational, and drug discovery research that will positively influence healthcare through the accelerated release and development of new and powerful therapeutics and diagnostics, consistent with the mission of the National Institutes of Health. PUBLIC HEALTH RELEVANCE: High Throughput, Label-Fee Molecular Interaction Platform for Membrane Protein Targets Drugs directed against cell membrane targets comprise one of the most important classes of therapeutics and focused pharmaceutical research. Tools available to support this research lack enabling capabilities, and are a barrier to progress. Our program will result in the creation of a novel research platform that will exert a substantial and powerful impact to advance progress in membrane target drug research, yielding new and improved therapeutics that will positively impact the treatment of disease, improving healthcare while reducing its cost.


Patent
Molecular Sensing, Inc. | Date: 2010-01-08

This invention provides methods and devices for analyzing interference patterns. The methods include fitting a Gaussian distribution to a cross correlation of two patterns from interferometric analysis of a liquid at a first and second time; identifying a positional shift of the pattern by comparing a selected value of the Gaussian distributions of the pattern at the first and second times; and determining a change in refractive index of the liquid from the positional shift. In another aspect, a method of extending the dynamic range of an interferometric data set is provided that comprises linearizing the data set, for example, using the arcsine function.


Patent
Vanderbilt University and Molecular Sensing, Inc. | Date: 2012-01-10

This invention provides an interferometric detection device configured to maintain a temperature of a sensing area to within 20 m C. of a first target temperature and to maintain a temperature of the medium within 500 m C. of a second target temperature The device can do so under conditions in which ambient temperature changes from 0.1 C. to 5 C. over 5 minutes.


Patent
Molecular Sensing, Inc. | Date: 2013-03-15

Methods and systems for improved chemical event detection from back scattering interferometry fringe data provide sensitive detection of a chemical event by more selectively analyzing fringe shift data.

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