02188nas a2200205   4500008004100000022001400041245010900055210006900164260001500233300001100248490000900259520154600268100002101814700001901835700001601854700001601870700001801886700002301904856005501927       2013                        ENG d  a0277-786X00aInstrument-free exothermic heating with phase change temperature control for paper microfluidic devices.0 aInstrumentfree exothermic heating with phase change temperature   c2013 Mar 9  a86150R0 v86153 a<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' 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°C.</p>1 aSingleton, Jered1 aZentner, Chris1 aBuser, Josh1 aYager, Paul1 aLaBarre, Paul1 aWeigl, Bernhard, H  uhttp://microfluidicsciences.com/drupal/?q=node/20501902nas a2200133   4500008004100000245007500041210006600116520127800182100002401460700001601484700002001500700001701520856023101537       2007                        eng d00aUnited {States} {Patent}: 7271007 - {Microscale} diffusion immunoassay0 aUnited States Patent 7271007 Microscale diffusion immunoassay3 aMethods 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.1 aWeigl, Bernhard, H.1 aYager, Paul1 aKamholz, Andrew1 aHatch, Anson  uhttp://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%2201463nas a2200289   4500008004100000022001400041245006700055210006600122260001600188300001000204490000800214520064300222653002500865653003000890653001100920653002100931653001800952653001800970100001600988700002001004700001401024700002001038700001801058700001901076700002301095856005501118       2006                        eng d  a1476-468700aMicrofluidic diagnostic technologies for global public health.0 aMicrofluidic diagnostic technologies for global public health  c2006 Jul 27  a412-80 v4423 a<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>10aDeveloping Countries10aDiagnostic Tests, Routine10aHumans10aInternationality10aMicrofluidics10aPublic Health1 aYager, Paul1 aEdwards, Thayne1 aFu, Elain1 aHelton, Kristen1 aNelson, Kjell1 aTam, Milton, R1 aWeigl, Bernhard, H  uhttp://microfluidicsciences.com/drupal/?q=node/22201922nas a2200145   4500008004100000245007500041210006600116260000800182520127800190100002401468700001601492700002001508700001701528856023101545       2003                        eng d00aUnited {States} {Patent}: 6541213 - {Microscale} diffusion immunoassay0 aUnited States Patent 6541213 Microscale diffusion immunoassay  capr3 aMethods 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.1 aWeigl, Bernhard, H.1 aYager, Paul1 aKamholz, Andrew1 aHatch, Anson  uhttp://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%2201903nas a2200253   4500008004100000245007800041210006900119260000800188520096500196100002401161700001601185700002101201700001901222700002201241700002001263700002301283700002001306700001901326700002001345700001801365700002001383700001501403856023101418       2002                        eng d00aUnited {States} {Patent}: 6454945 - {Microfabricated} devices and methods0 aUnited States Patent 6454945 Microfabricated devices and methods  csep3 aThis 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.1 aWeigl, Bernhard, H.1 aYager, Paul1 aBrody, James, P.1 aHoll, Mark, R.1 aForster, Fred, K.1 aAltendorf, Eric1 aGalambos, Paul, C.1 aKenny, Margaret1 aSchutte, David1 aHixson, Gregory1 aZebert, Diane1 aKamholz, Andrew1 aWu, Caicai  uhttp://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%2202069nas a2200133   4500008004100000245009700041210006900138520142200207100001501629700002001644700002401664700001601688856023101704       2001                        eng d00aUnited {States} {Patent}: 6221677 - {Simultaneous} particle separation and chemical reaction0 aUnited States Patent 6221677 Simultaneous particle separation an3 aThis 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.1 aWu, Caicai1 aWeigl, Bernhard1 aKenny, Margaret, A.1 aYager, Paul  uhttp://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%2202089nas a2200145   4500008004100000245009700041210006900138260000800207520142200215100001501637700002001652700002401672700001601696856023101712       2001                        eng d00aUnited {States} {Patent}: 6297061 - {Simultaneous} particle separation and chemical reaction0 aUnited States Patent 6297061 Simultaneous particle separation an  coct3 aThis 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.1 aWu, Caicai1 aWeigl, Bernhard1 aKenny, Margaret, A.1 aYager, Paul  uhttp://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%2202085nas a2200133   4500008004100000245013400041210006900175260000800244520141100252100002001663700001601683700002101699856023101720       2000                        eng d00aUnited {States} {Patent}: 6159739 - {Device} and method for 3-dimensional alignment of particles in microfabricated flow channels0 aUnited States Patent 6159739 Device and method for 3dimensional   cdec3 aThe 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.1 aWeigl, Bernhard1 aYager, Paul1 aBrody, James, P.  uhttp://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%2201808nas a2200229   4500008004100000245009000041210006900131260000800200520092700208100002401135700001601159700002101175700001901196700002001215700001901235700002001254700001801274700002001292700001501312700002001327856023101347       1999                        eng d00aUnited {States} {Patent}: 5972710 - {Microfabricated} diffusion-based chemical sensor0 aUnited States Patent 5972710 Microfabricated diffusionbased chem  coct3 aA 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.1 aWeigl, Bernhard, H.1 aYager, Paul1 aBrody, James, P.1 aHoll, Mark, R.1 aKenny, Margaret1 aSchutte, David1 aHixson, Gregory1 aZebert, Diane1 aKamholz, Andrew1 aWu, Caicai1 aAltendorf, Eric  uhttp://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%2201613nas a2200145   4500008004100000245009000041210006900131260000800200520094800208100001601156700002401172700002101196700001901217856023101236       1998                        eng d00aUnited {States} {Patent}: 5716852 - {Microfabricated} diffusion-based chemical sensor0 aUnited States Patent 5716852 Microfabricated diffusionbased chem  cfeb3 aA 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.1 aYager, Paul1 aWeigl, Bernhard, H.1 aBrody, James, P.1 aHoll, Mark, R.  uhttp://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