01710nas a2200145   4500008004100000245013300041210006900174520099400243100002401237700001901261700001801280700002001298700001501318856023101333       2003                        eng d00aUnited {States} {Patent}: 6582963 - {Simultaneous} analyte determination and reference balancing in reference {T}-sensor devices0 aUnited States Patent 6582963 Simultaneous analyte determination 3 aA reference T-sensor system is provided for detecting the presence and/or measuring the concentration of analyte particles in a sample stream. The system includes: a) a laminar flow channel; b) three or more inlets in fluid connection with the laminar flow channel for respectively conducting into the laminar flow channel (1) an indicator stream which may include an indicator substance which indicates the presence of analyte particles by a detectable change in property when contacted with the analyte particles, (2) the sample stream, and (3) a reference stream, which can be a control stream and/or an internal standard stream; c) wherein the laminar flow channel has a depth and/or width 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 form a detection area; and (d) an outlet for conducting the streams out of the laminar flow channel preferably to form a single mixed stream.1 aWeigl, Bernhard, H.1 aHoll, Mark, R.1 aZebert, Diane1 aKenny, Margaret1 aWu, Caicai  uhttp://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearch-bool.html&r=21&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%2202375nas a2200157   4500008004100000245013300041210006900174260000800243520163900251100002401890700001901914700001801933700002001951700001501971856023101986       2001                        eng d00aUnited {States} {Patent}: 6171865 - {Simultaneous} analyte determination and reference balancing in reference {T}-sensor devices0 aUnited States Patent 6171865 Simultaneous analyte determination   cjan3 aA reference sensor system is provided for detecting the presence and/or measuring the concentration of analyte particles in a sample stream. The system includes: a) a laminar flow channel; b) three or more inlet means in fluid connection with the laminar flow channel for respectively conducting into the laminar flow channel (1) an indicator stream which may include an indicator substance which indicates the presence of the analyte particles, (2) the sample stream, and (3) a reference stream, which can be a control stream and/or internal standard stream; and, c) wherein the laminar flow channel has a depth and/or width sufficiently small to allow laminar flow of said streams and a length sufficient to allow particles of the analyte to diffuse into the indicator stream to form a detection area. Branching channels may be provided as outlet means for conducting the streams out of the laminar flow channel. Also provided are methods of using the device to improve accuracy and increase convenience of measuring the concentration of analytes in a sample. Monitoring reference stream(s) in laminar flow with sample stream(s) allows for calibration or for monitoring or correcting for the effects of experimental conditions which might otherwise degrade accuracy. A reference stream which serves as both a control stream and an internal standard stream is convenient and economical. The device of this invention also needs less frequent calibration than previously-known fluid analysis devices because the devices and methods of this invention provide for continuous and simultaneous quality control and internal standardization.1 aWeigl, Bernhard, H.1 aHoll, Mark, R.1 aZebert, Diane1 aKenny, Margaret1 aWu, Caicai  uhttp://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearch-bool.html&r=30&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%2202381nas a2200157   4500008004100000245013300041210006900174260000800243520164500251100002401896700001901920700001801939700002001957700001501977856023101992       1999                        eng d00aUnited {States} {Patent}: 5948684 - {Simultaneous} analyte determination and reference balancing in reference {T}-sensor devices0 aUnited States Patent 5948684 Simultaneous analyte determination   csep3 aA reference T-sensor system is provided for detecting the presence and/or measuring the concentration of analyte particles in a sample stream. The system includes: a) a laminar flow channel; b) three or more inlet means in fluid connection with the laminar flow channel for respectively conducting into the laminar flow channel (1) an indicator stream which may include an indicator substance which indicates the presence of the analyte particles, (2) the sample stream, and (3) a reference stream, which can be a control stream and/or internal standard stream; c) wherein the laminar flow channel has a depth and/or width 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 form a detection area; and d) outlet means for conducting the streams out of the laminar flow channel preferably to form a single mixed stream. Also provided are methods of using the device to improve accuracy and increase convenience of measuring the concentration of analytes in a sample. Monitoring reference stream(s) in laminar flow with sample stream(s) allows for calibration or for monitoring or correcting for the effects of experimental conditions which might otherwise degrade accuracy. A reference stream which serves as both a control stream and an internal standard stream is convenient and economical. The device of this invention also needs less frequent calibration than previously-known fluid analysis devices because the devices and methods of this invention provide for continuous and simultaneous quality control and internal standardization.1 aWeigl, Bernhard, H.1 aHoll, Mark, R.1 aZebert, Diane1 aKenny, Margaret1 aWu, Caicai  uhttp://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearch-bool.html&r=37&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%22