@article {205,
	title = {Instrument-free exothermic heating with phase change temperature control for paper microfluidic devices.},
	journal = {Proc SPIE Int Soc Opt Eng},
	volume = {8615},
	year = {2013},
	month = {2013 Mar 9},
	pages = {86150R},
	abstract = {<p>Many infectious diseases, as well as some cancers, that affect global health are most accurately diagnosed through nucleic acid amplification and detection. There is a great need to simplify nucleic acid-based assay systems for use in global health in low-resource settings as well as in settings that do not have convenient access to laboratory staff and equipment such as doctors{\textquoteright} offices and home care settings. In developing countries, unreliable electric power, inadequate supply chains, and lack of maintenance for complex diagnostic instruments are all common infrastructure shortfalls. Many elements of instrument-free, disposable, nucleic acid amplification assays have been demonstrated in recent years. However, the problem of instrument-free, low-cost, temperature-controlled chemical heating remains unsolved. In this paper we present the current status and results of work towards developing disposable, low-cost, temperature-controlled heaters designed to support isothermal nucleic acid amplification assays that are integrated with a two-dimensional paper network. Our approach utilizes the heat generated through exothermic chemical reactions and controls the heat through use of engineered phase change materials to enable sustained temperatures required for nucleic acid amplification. By selecting appropriate exothermic and phase change materials, temperatures can be controlled over a wide range, suitable for various isothermal amplification methods, and maintained for over an hour at an accuracy of +/- 1{\textdegree}C.</p>},
	issn = {0277-786X},
	doi = {10.1117/12.2005928},
	author = {Singleton, Jered and Zentner, Chris and Buser, Josh and Yager, Paul and LaBarre, Paul and Weigl, Bernhard H}
}
@patent {weigl_united_2007-1,
	title = {United {States} {Patent}: 7271007 - {Microscale} diffusion immunoassay},
	number = {7271007},
	year = {2007},
	abstract = {Methods and apparatuses are provided for determining presence and concentration of analytes by exploiting molecular binding reactions and differential diffusion rates. Analyte particles and binding particles are allowed to diffuse toward each other, and slowing of the diffusion front is detected when they meet. From the position of the diffusion front, presence and concentration of analyte particles can be determined. One embodiment provides a competitive immunoassay in a microfluidic format. This diffusion immunoassay (DIA) relies on measuring the concentration of labeled antigen along one dimension of a microchannel after allowing it to diffuse for a short time into a region containing specific antibodies. A simple microfluidic device, the T-Sensor, was used to implement a DIA to measure the concentration of phenytoin, a small drug molecule. Concentrations of analyte over the range of 50 to 1600 nM can be measured in less than a minute. The assay is homogeneous, rapid, requires only microliter volumes of reagents and sample, and is applicable to a wide range of analytes, including therapeutic drugs, molecular biological markers, and environmental contaminants. Methods for separating particles of similar size in a diffusion separator are also provided.},
	url = {http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2\&Sect2=HITOFF\&p=1\&u=\%2Fnetahtml\%2FPTO\%2Fsearch-bool.html\&r=14\&f=G\&l=50\&co1=AND\&d=PTXT\&s1=\%22Weigl\%3B+Bernhard\%22.INNM.\&OS=IN/\%22Weigl;+Bernhard\%22\&RS=IN/\%22Weigl;+Bernhard\%22},
	author = {Weigl, Bernhard H. and Yager, Paul and Kamholz, Andrew and Hatch, Anson}
}
@article {222,
	title = {Microfluidic diagnostic technologies for global public health.},
	journal = {Nature},
	volume = {442},
	year = {2006},
	month = {2006 Jul 27},
	pages = {412-8},
	abstract = {<p>The developing world does not have access to many of the best medical diagnostic technologies; they were designed for air-conditioned laboratories, refrigerated storage of chemicals, a constant supply of calibrators and reagents, stable electrical power, highly trained personnel and rapid transportation of samples. Microfluidic systems allow miniaturization and integration of complex functions, which could move sophisticated diagnostic tools out of the developed-world laboratory. These systems must be inexpensive, but also accurate, reliable, rugged and well suited to the medical and social contexts of the developing world.</p>},
	keywords = {Developing Countries, Diagnostic Tests, Routine, Humans, Internationality, Microfluidics, Public Health},
	issn = {1476-4687},
	doi = {10.1038/nature05064},
	author = {Yager, Paul and Edwards, Thayne and Fu, Elain and Helton, Kristen and Nelson, Kjell and Tam, Milton R and Weigl, Bernhard H}
}
@patent {weigl_united_2003-2,
	title = {United {States} {Patent}: 6541213 - {Microscale} diffusion immunoassay},
	number = {6541213},
	year = {2003},
	month = {apr},
	abstract = {Methods and apparatuses are provided for determining presence and concentration of analytes by exploiting molecular binding reactions and differential diffusion rates. Analyte particles and binding particles are allowed to diffuse toward each other, and slowing of the diffusion front is detected when they meet. From the position of the diffusion front, presence and concentration of analyte particles can be determined. One embodiment provides a competitive immunoassay in a microfluidic format. This diffusion immunoassay (DIA) relies on measuring the concentration of labeled antigen along one dimension of a microchannel after allowing it to diffuse for a short time into a region containing specific antibodies. A simple microfluidic device, the T-Sensor, was used to implement a DIA to measure the concentration of phenytoin, a small drug molecule. Concentrations of analyte over the range of 50 to 1600 nM can be measured in less than a minute. The assay is homogeneous, rapid, requires only microliter volumes of reagents and sample, and is applicable to a wide range of analytes, including therapeutic drugs, molecular biological markers, and environmental contaminants. Methods for separating particles of similar size in a diffusion separator are also provided.},
	url = {http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2\&Sect2=HITOFF\&p=1\&u=\%2Fnetahtml\%2FPTO\%2Fsearch-bool.html\&r=23\&f=G\&l=50\&co1=AND\&d=PTXT\&s1=\%22Weigl\%3B+Bernhard\%22.INNM.\&OS=IN/\%22Weigl;+Bernhard\%22\&RS=IN/\%22Weigl;+Bernhard\%22},
	author = {Weigl, Bernhard H. and Yager, Paul and Kamholz, Andrew and Hatch, Anson}
}
@patent {weigl_united_2002-2,
	title = {United {States} {Patent}: 6454945 - {Microfabricated} devices and methods},
	number = {6454945},
	year = {2002},
	month = {sep},
	abstract = {This invention provides microfabricated systems for extraction of desired particles from a sample stream containing desired and undesired particles. The sample stream is placed in laminar flow contact with an extraction stream under conditions in which inertial effects are negligible. The contact between the two streams is maintained for a sufficient period of time to allow differential transport of the desired particles from the sample stream into the extraction stream. In a preferred embodiment the differential transport mechanism is diffusion. The extraction system of this invention coupled to a microfabricated diffusion-based mixing device and/or sensing means allows picoliter quantities of fluid to be processed or analyzed on devices no larger than silicon wafers. Such diffusion-based mixing or sensing devices are preferably channel cell systems for detecting the presence and/or measuring the quantity of analyte particles in a sample stream.},
	url = {http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2\&Sect2=HITOFF\&p=1\&u=\%2Fnetahtml\%2FPTO\%2Fsearch-bool.html\&r=25\&f=G\&l=50\&co1=AND\&d=PTXT\&s1=\%22Weigl\%3B+Bernhard\%22.INNM.\&OS=IN/\%22Weigl;+Bernhard\%22\&RS=IN/\%22Weigl;+Bernhard\%22},
	author = {Weigl, Bernhard H. and Yager, Paul and Brody, James P. and Holl, Mark R. and Forster, Fred K. and Altendorf, Eric and Galambos, Paul C. and Kenny, Margaret and Schutte, David and Hixson, Gregory and Zebert, Diane and Kamholz, Andrew and Wu, Caicai}
}
@patent {wu_united_2001,
	title = {United {States} {Patent}: 6221677 - {Simultaneous} particle separation and chemical reaction},
	number = {6221677},
	year = {2001},
	abstract = {This invention provides a method and apparatus for detecting the presence of analyte particles in a sample fluid also comprising larger particles, particularly blood. It exploits diffusion to provide simultaneous filtering of the larger particles and reaction of the analyte particles. A sample stream and a reagent stream join on the upstream end of a laminar flow reaction channel and flow in adjacent laminar streams. The reagents can be in solution or immobilized on a bead. The analyte particles diffuse from the sample stream into the reagent stream, leaving behind the larger particles in the residual sample stream. In the reagent stream the analyte particles react with reagent particles and form product particles, thereby creating a product stream. At the downstream end of the reaction channel, the residual sample stream and the product stream are divided. The product particles are then detected, preferably optically, in the product stream. Prior to detection, the product stream can undergo further filtering or separation, or can join a second reagent stream to form secondary product particles. This apparatus and method can be used to implement competitive immunoassays or sandwich immunoassays using enzymatically or fluorescently labeled immunoreagents. The apparatus and method can also be used to synthesize products, in which case two reagent streams join in the laminar flow reaction channel.},
	url = {http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2\&Sect2=HITOFF\&p=1\&u=\%2Fnetahtml\%2FPTO\%2Fsearch-bool.html\&r=29\&f=G\&l=50\&co1=AND\&d=PTXT\&s1=\%22Weigl\%3B+Bernhard\%22.INNM.\&OS=IN/\%22Weigl;+Bernhard\%22\&RS=IN/\%22Weigl;+Bernhard\%22},
	author = {Wu, Caicai and Weigl, Bernhard and Kenny, Margaret A. and Yager, Paul}
}
@patent {wu_united_2001-1,
	title = {United {States} {Patent}: 6297061 - {Simultaneous} particle separation and chemical reaction},
	number = {6297061},
	year = {2001},
	month = {oct},
	abstract = {This invention provides a method and apparatus for detecting the presence of analyte particles in a sample fluid also comprising larger particles, particularly blood. It exploits diffusion to provide simultaneous filtering of the larger particles and reaction of the analyte particles. A sample stream and a reagent stream join on the upstream end of a laminar flow reaction channel and flow in adjacent laminar streams. The reagents can be in solution or immobilized on a bead. The analyte particles diffuse from the sample stream into the reagent stream, leaving behind the larger particles in the residual sample stream. In the reagent stream the analyte particles react with reagent particles and form product particles, thereby creating a product stream. At the downstream end of the reaction channel, the residual sample stream and the product stream are divided. The product particles are then detected, preferably optically, in the product stream. Prior to detection, the product stream can undergo further filtering or separation, or can join a second reagent stream to form secondary product particles. This apparatus and method can be used to implement competitive immunoassays or sandwich immunoassays using enzymatically or fluorescently labeled immunoreagents. The apparatus and method can also be used to synthesize products, in which case two reagent streams join in the laminar flow reaction channel.},
	url = {http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2\&Sect2=HITOFF\&p=1\&u=\%2Fnetahtml\%2FPTO\%2Fsearch-bool.html\&r=27\&f=G\&l=50\&co1=AND\&d=PTXT\&s1=\%22Weigl\%3B+Bernhard\%22.INNM.\&OS=IN/\%22Weigl;+Bernhard\%22\&RS=IN/\%22Weigl;+Bernhard\%22},
	author = {Wu, Caicai and Weigl, Bernhard and Kenny, Margaret A. and Yager, Paul}
}
@patent {weigl_united_2000-1,
	title = {United {States} {Patent}: 6159739 - {Device} and method for 3-dimensional alignment of particles in microfabricated flow channels},
	number = {6159739},
	year = {2000},
	month = {dec},
	abstract = {The present invention provides a sheath flow module made from a first plate of material having formed therein a laminar fluid flow channel; at least two inlets, each inlet joining the laminar flow channel at a junction, the first inlet junction being wider than the second inlet junction, and an outlet from the flow channel. A second plate, e.g. a transparent cover plate, seals the module and allows for optical measurements. A first inlet allows for introduction of a first fluid into the flow channel. The first fluid is the sheath fluid. A second inlet allows for introduction of a second fluid into the sheath fluid while it is flowing through the flow channel. The second fluid is the center fluid. Because the second inlet junction is narrower than the first inlet junction, the center fluid becomes surrounded on both sides by the sheath fluid. After all fluids have been introduced and sheath flow has been achieved, the depth of the flow channel can be decreased, leading to vertical hydrodynamic focusing. Optionally, the width of the flow channel can be decreased, leading to horizontal hydrodynamic focusing. The decrease in depth and width can be gradual or abrupt. The device of the present invention can function in two modes, the sheath flow mode and the particle injector mode, depending on the relative densities of the sheath fluid, the center fluid, and any particles in either fluid.},
	url = {http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2\&Sect2=HITOFF\&p=1\&u=\%2Fnetahtml\%2FPTO\%2Fsearch-bool.html\&r=31\&f=G\&l=50\&co1=AND\&d=PTXT\&s1=\%22Weigl\%3B+Bernhard\%22.INNM.\&OS=IN/\%22Weigl;+Bernhard\%22\&RS=IN/\%22Weigl;+Bernhard\%22},
	author = {Weigl, Bernhard and Yager, Paul and Brody, James P.}
}
@patent {weigl_united_1999-1,
	title = {United {States} {Patent}: 5972710 - {Microfabricated} diffusion-based chemical sensor},
	number = {5972710},
	year = {1999},
	month = {oct},
	abstract = {A channel-cell system is provided for detecting the presence and/or measuring the presence of analyte particles in a sample stream comprising: a) a laminar flow channel; b) two inlets in fluid connection with the laminar flow channel for respectively conducting into the laminar flow channel (1) an indicator stream which may comprise an indicator substance which indicates the presence of the analyte particles by a detectable change in property when contacted with the analyte particles, and (2) the sample stream; c) wherein the laminar flow channel has a depth sufficiently small to allow laminar flow of the streams and a length sufficient to allow particles of the analyte to diffuse into the indicator stream to the substantial exclusion of the larger particles in the sample stream to form a detection area; and d) an outlet for conducting the streams out of the laminar flow channel to form a single mixed stream.},
	url = {http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2\&Sect2=HITOFF\&p=1\&u=\%2Fnetahtml\%2FPTO\%2Fsearch-bool.html\&r=36\&f=G\&l=50\&co1=AND\&d=PTXT\&s1=\%22Weigl\%3B+Bernhard\%22.INNM.\&OS=IN/\%22Weigl;+Bernhard\%22\&RS=IN/\%22Weigl;+Bernhard\%22},
	author = {Weigl, Bernhard H. and Yager, Paul and Brody, James P. and Holl, Mark R. and Kenny, Margaret and Schutte, David and Hixson, Gregory and Zebert, M. Diane and Kamholz, Andrew and Wu, Caicai and Altendorf, Eric}
}
@patent {yager_united_1998,
	title = {United {States} {Patent}: 5716852 - {Microfabricated} diffusion-based chemical sensor},
	number = {5716852},
	year = {1998},
	month = {feb},
	abstract = {A channel-cell system is provided for detecting the presence and/or measuring the presence of analyte particles in a sample stream comprising: a) a laminar flow channel; b) two inlet means in fluid connection with said laminar flow channel for respectively conducting into said laminar flow channel (1) an indicator stream which may comprise an indicator substance which indicates the presence of said analyte particles by a detectable change in property when contacted with said analyte particles, and (2) said sample stream; c) wherein said laminar flow channel has a depth sufficiently small to allow laminar flow of said streams and a length sufficient to allow particles of said analyte to diffuse into said indicator stream to the substantial exclusion of said larger particles in said sample stream to form a detection area; and d) outlet means for conducting said streams out of said laminar flow channel to form a single mixed stream.},
	url = {http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2\&Sect2=HITOFF\&p=1\&u=\%2Fnetahtml\%2FPTO\%2Fsearch-bool.html\&r=39\&f=G\&l=50\&co1=AND\&d=PTXT\&s1=\%22Weigl\%3B+Bernhard\%22.INNM.\&OS=IN/\%22Weigl;+Bernhard\%22\&RS=IN/\%22Weigl;+Bernhard\%22},
	author = {Yager, Paul and Weigl, Bernhard H. and Brody, James P. and Holl, Mark R.}
}
