@article {212, title = {A highly sensitive rapid diagnostic test for Chagas disease that utilizes a recombinant Trypanosoma cruzi antigen.}, journal = {IEEE Trans Biomed Eng}, volume = {58}, year = {2011}, month = {2011 Mar}, pages = {814-7}, abstract = {

Improved diagnostic tests for Chagas disease are urgently needed. A new lateral flow rapid test for Chagas disease is under development at PATH, in collaboration with Laboratorio Lemos of Argentina, which utilizes a recombinant antigen for detection of antibodies to Trypanosoma cruzi. To evaluate the performance of this test, 375 earlier characterized serum specimens from a region where Chagas is endemic were tested using a reference test (the Ortho T. cruzi ELISA, Johnson \& Johnson), a commercially available rapid test (Chagas STAT-PAK, Chembio), and the PATH-Lemos rapid test. Compared to the composite reference tests, the PATH-Lemos rapid test demonstrated an optimal sensitivity of 99.5\% and specificity of 96.8\%, while the Chagas STAT-PAK demonstrated a sensitivity of 95.3\% and specificity of 99.5\%. These results indicate that the PATH-Lemos rapid test shows promise as an improved and reliable tool for screening and diagnosis of Chagas disease.

}, keywords = {Antibodies, Protozoan, Antigens, Protozoan, Chagas Disease, Humans, Immunoassay, Point-of-Care Systems, Recombinant Proteins, Sensitivity and Specificity, Trypanosoma cruzi}, issn = {1558-2531}, doi = {10.1109/TBME.2010.2087334}, author = {Barfield, C A and Barney, R S and Crudder, C H and Wilmoth, J L and Stevens, D S and Mora-Garcia, S and Yanovsky, M J and Weigl, B H and Yanovsky, J} } @article {217, title = {Simplicity of use: a critical feature for widespread adoption of diagnostic technologies in low-resource settings.}, journal = {Expert Rev Med Devices}, volume = {6}, year = {2009}, month = {2009 Sep}, pages = {461-4}, keywords = {Biotechnology, Diagnostic Imaging, Human Engineering, Internationality, Quality Assurance, Health Care}, issn = {1745-2422}, doi = {10.1586/erd.09.31}, author = {Weigl, B H and Boyle, D S and de los Santos, T and Peck, R B and Steele, M S} } @article {224, title = {Initial study of using a laminar fluid diffusion interface for sample preparation in high-performance liquid chromatography.}, journal = {J Chromatogr A}, volume = {954}, year = {2002}, month = {2002 Apr 19}, pages = {33-40}, abstract = {

This report describes a new microfluidic device called the H Filter for sample preparation prior to HPLC. The H Filters make possible a diffusional transfer of an analyte from a sample stream into a stream of a "receiver" fluid. Existing mathematical models can be used for optimizing experimental conditions. The authors have selected the extraction of the antibiotic cephradine from blood to demonstrate the utility of the new device. The extracts of blood samples spiked with cephradine levels between 0.2 and 100 microg/ml were analyzed using a C8 reversed-phase column and UV detection at 260 nm. The HPLC results were in good agreement with theory. The recovery of 32.2+/-2.8\% was uniform over the entire range of cephradine concentrations. The new method completely avoids the use of centrifuges, that is otherwise typical for most current methodologies for the preparation of blood samples prior to HPLC analysis.

}, keywords = {Cephradine, Chromatography, High Pressure Liquid, Diffusion, Humans, Reference Standards, Spectrophotometry, Ultraviolet}, issn = {0021-9673}, author = {Jandik, P and Weigl, B H and Kessler, N and Cheng, J and Morris, C J and Schulte, T and Avdalovic, N} } @article {227, title = {Lab-on-a-chip sample preparation using laminar fluid diffusion interfaces--computational fluid dynamics model results and fluidic verification experiments.}, journal = {Fresenius J Anal Chem}, volume = {371}, year = {2001}, month = {2001 Sep}, pages = {97-105}, abstract = {

Microfluidic structures for the generation of laminar fluid diffusion interfaces (LFDIs) for sample preparation and analysis are discussed. Experimental data and the results of fluid modeling are shown. LFDIs are generated when two or more streams flow in parallel in a single microfluidic structure without any mixing of the fluids other than by diffusion of particles across the diffusion interface. It has been shown that such structures can be used for diffusion-based separation and detection applications. The method has been applied to DNA desalting, the extraction of small proteins from whole blood samples, and the detection of various constituents in whole blood, among other examples. In this paper the design and manufacture of self-contained microfluidic cartridges for the extraction of small molecules from a mixture of small and large molecules by diffusion is demonstrated. The cards are operated without any external instrumentation, and use hydrostatic pressure as the driving force. The performance of the cartridges is illustrated by separating fluorescein from a mixture of fluorescein and dextran of molecular weight 2 x 10(6). In a single pass, 98.6\% of dextran was retained in the product whereas 43.1\% of fluorescein was removed. The method is adjustable for different separation requirements, and computational fluid dynamics (CFD) models are shown that demonstrate the tuning of various microfluidic parameters to optimize separation performance. Other applications of LFDIs for establishment of stable concentration gradients, and the exposure of chemical constituents or biological particles to these concentration gradients are shown qualitatively. Microfluidic chips have been designed for high-throughput screening applications that enable the uniform and controlled exposure of cells to lysing agents, thus enabling the differentiation of cells by their sensitivity to specific agents in an on-chip cytometer coupled directly to the lysing structure.

}, keywords = {Chemistry Techniques, Analytical, Dextrans, Diffusion, Equipment Design, Fluorescein, Microchemistry, Models, Chemical, Molecular Weight, Rheology, Viscosity}, issn = {0937-0633}, author = {Weigl, B H and Bardell, R L and Kesler, N and Morris, C J} } @article {228, title = {A rapid diffusion immunoassay in a T-sensor.}, journal = {Nat Biotechnol}, volume = {19}, year = {2001}, month = {2001 May}, pages = {461-5}, abstract = {

We have developed a rapid diffusion immunoassay that allows measurement of small molecules down to subnanomolar concentrations in <1 min. This competitive assay is based on measuring the distribution of a labeled probe molecule after it diffuses for a short time from one region into another region containing antigen-specific antibodies. The assay was demonstrated in the T-sensor, a simple microfluidic device that places two fluid streams in contact and allows interdiffusion of their components. The model analyte was phenytoin, a typical small drug molecule. Clinically relevant levels were measured in blood diluted from 10- to 400-fold in buffer containing the labeled antigen. Removal of cells from blood samples was not necessary. This assay compared favorably with fluorescence polarization immunoassay (FPIA) measurements. Numerical simulations agree well with experimental results and provide insight for predicting assay performance and limitations. The assay is homogeneous, requires <1 microl of reagents and sample, and is applicable to a wide range of analytes.

}, keywords = {Antibody Specificity, Antigen-Antibody Complex, Binding, Competitive, Diffusion, Fluorescence Polarization Immunoassay, Immunoassay, Molecular Weight, Phenytoin, Rheology}, issn = {1087-0156}, doi = {10.1038/88135}, author = {Hatch, A and Kamholz, A E and Hawkins, K R and Munson, M S and Schilling, E A and Weigl, B H and Yager, P} } @article {229, title = {Quantitative analysis of molecular interaction in a microfluidic channel: the T-sensor.}, journal = {Anal Chem}, volume = {71}, year = {1999}, month = {1999 Dec 1}, pages = {5340-7}, abstract = {

The T-sensor is a recently developed microfluidic chemical measurement device that exploits the low Reynolds number flow conditions in microfabricated channels. The interdiffusion and resulting chemical interaction of components from two or more input fluid streams can be monitored optically, allowing measurement of analyte concentrations on a continuous basis. In a simple form of T-sensor, the concentration of a target analyte is determined by measuring fluorescence intensity in a region where the analyte and a fluorescent indicator have interdiffused. An analytical model has been developed that predicts device behavior from the diffusion coefficients of the analyte, indicator, and analyte--indicator complex and from the kinetics of the complex formation. Diffusion coefficients depend on the local viscosity which, in turn, depends on local concentrations of all analytes. These relationships, as well as reaction equilibria, are often unknown. A rapid method for determining these unknown parameters by interpreting T-sensor experiments through the model is presented.

}, keywords = {Kinetics, Models, Chemical, Spectrometry, Fluorescence}, issn = {0003-2700}, author = {Kamholz, A E and Weigl, B H and Finlayson, B A and Yager, P} } @article {231, title = {Capillary waveguide optrodes: an approach to optical sensing in medical diagnostics.}, journal = {Appl Opt}, volume = {35}, year = {1996}, month = {1996 Jul 1}, pages = {3426-31}, abstract = {

Glass capillaries with a chemically sensitive coating on the inner surface are used as optical sensors for medical diagnostics. A capillary simultaneously serves as a sample compartment, a sensor element, and an inhomogeneous optical waveguide. Various detection schemes based on absorption, fluorescence intensity, or fluorescence lifetime are described. In absorption-based capillary waveguide optrodes the absorption in the sensor layer is analyte dependent; hence light transmission along the inhomogeneous waveguiding structure formed by the capillary wall and the sensing layer is a function of the analyte concentration. Similarly, in fluorescence-based capillary optrodes the fluorescence intensity or the fluorescence lifetime of an indicator dye fixed in the sensing layer is analyte dependent; thus the specific property of fluorescent light excited in the sensing layer and thereafter guided along the inhomogeneous waveguiding structure is a function of the analyte concentration. Both schemes are experimentally demonstrated, one with carbon dioxide as the analyte and the other one with oxygen. The device combines optical sensors with the standard glass capillaries usually applied to gather blood drops from fingertips, to yield a versatile diagnostic instrument, integrating the sample compartment, the optical sensor, and the light-collecting optics into a single piece. This ensures enhanced sensor performance as well as improved handling compared with other sensors.

}, issn = {0003-6935}, doi = {10.1364/AO.35.003426}, author = {Lippitsch, M E and Draxler, S and Kieslinger, D and Lehmann, H and Weigl, B H} } @article {232, title = {Optical triple sensor for measuring pH, oxygen and carbon dioxide.}, journal = {J Biotechnol}, volume = {32}, year = {1994}, month = {1994 Feb 14}, pages = {127-38}, abstract = {

A triple sensor unit consisting of opto-chemical sensors for measurement of pH, oxygen and carbon dioxide in bioreactors is presented. The pH and the CO2 sensor are based on the color change of a pH-sensitive dye immobilized on a polymeric support. The resulting changes in absorption are monitored through optical fibers. The oxygen sensor is based on the quenching of the fluorescence of a metal-organic dye. All three sensors are fully LED compatible. The sensitive membranes consist of plastic films and can be stored and replaced conveniently. The sensors are sterilizable with hydrogen peroxide and ethanol. In addition, the pH sensor is steam sterilizable. Accuracy, resolution and reproducibility fulfill the requirements for use in biotechnological applications. Calibration procedures for each sensor are presented. The working principle and the performance of all three sensors are described, with particular emphasis given to their application in bioreactors.

}, keywords = {Carbon Dioxide, Hydrogen-Ion Concentration, Oxygen}, issn = {0168-1656}, author = {Weigl, B H and Holobar, A and Trettnak, W and Klimant, I and Kraus, H and O{\textquoteright}Leary, P and Wolfbeis, O S} }