FLUORESCENT DYES FOR USE IN GLUCOSE SENSING
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Abstract
A novel class of compounds that includes HPTS-Cys-MA, and methods of making them are disclosed herein. The class of compounds including HPTS-Cys-MA are useful as fluorescent dyes for analyte detection.
331 Citations
Transcutaneous analyte sensor | ||
Patent #
US 7,885,697 B2
Filed 03/10/2005
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Optimized sensor geometry for an implantable glucose sensor | ||
Patent #
US 7,881,763 B2
Filed 05/02/2006
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Low oxygen in vivo analyte sensor | ||
Patent #
US 7,899,511 B2
Filed 01/17/2006
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Transcutaneous analyte sensor | ||
Patent #
US 7,905,833 B2
Filed 06/21/2005
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Low oxygen in vivo analyte sensor | ||
Patent #
US 7,901,354 B2
Filed 05/01/2008
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Transcutaneous analyte sensor | ||
Patent #
US 7,946,984 B2
Filed 03/10/2005
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Transcutaneous analyte sensor | ||
Patent #
US 7,949,381 B2
Filed 04/11/2008
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
System and methods for processing analyte sensor data for sensor calibration | ||
Patent #
US 7,920,906 B2
Filed 03/09/2006
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Integrated receiver for continuous analyte sensor | ||
Patent #
US 7,927,274 B2
Filed 07/29/2008
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Systems and methods for replacing signal artifacts in a glucose sensor data stream | ||
Patent #
US 8,010,174 B2
Filed 08/22/2003
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Systems and methods for replacing signal artifacts in a glucose sensor data stream | ||
Patent #
US 7,998,071 B2
Filed 10/14/2009
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Signal processing for continuous analyte sensor | ||
Patent #
US 8,005,524 B2
Filed 03/24/2010
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Integrated delivery device for continuous glucose sensor | ||
Patent #
US 7,976,492 B2
Filed 08/06/2009
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
System and methods for processing analyte sensor data | ||
Patent #
US 8,052,601 B2
Filed 08/20/2008
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte sensing biointerface | ||
Patent #
US 8,060,174 B2
Filed 04/14/2006
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
System and methods for processing analyte sensor data | ||
Patent #
US 8,060,173 B2
Filed 08/01/2003
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Device and method for determining analyte levels | ||
Patent #
US 7,792,562 B2
Filed 12/22/2009
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Low oxygen in vivo analyte sensor | ||
Patent #
US 7,771,352 B2
Filed 05/01/2008
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Dual electrode system for a continuous analyte sensor | ||
Patent #
US 7,831,287 B2
Filed 04/28/2008
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
System and methods for processing analyte sensor data | ||
Patent #
US 7,826,981 B2
Filed 01/18/2005
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
System and methods for processing analyte sensor data | ||
Patent #
US 7,797,028 B2
Filed 04/14/2008
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
DEVICE AND METHOD FOR DETERMINING ANALYTE LEVELS | ||
Patent #
US 20100099970A1
Filed 12/22/2009
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Transcutaneous medical device with variable stiffness | ||
Patent #
US 7,783,333 B2
Filed 03/10/2005
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte sensor | ||
Patent #
US 7,828,728 B2
Filed 02/14/2007
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte sensor | ||
Patent #
US 7,857,760 B2
Filed 02/22/2006
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Systems and methods for replacing signal artifacts in a glucose sensor data stream | ||
Patent #
US 8,073,519 B2
Filed 10/14/2009
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Systems and methods for replacing signal artifacts in a glucose sensor data stream | ||
Patent #
US 8,073,520 B2
Filed 05/25/2010
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Use of an equilibrium intravascular sensor to achieve tight glycemic control | ||
Patent #
US 8,088,097 B2
Filed 11/20/2008
|
Current Assignee
Medtronic Minimed Incorporated
|
Original Assignee
GluMetrics Inc.
|
Porous membranes for use with implantable devices | ||
Patent #
US 8,118,877 B2
Filed 01/17/2007
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Systems and methods for replacing signal artifacts in a glucose sensor data stream | ||
Patent #
US 8,128,562 B2
Filed 10/14/2009
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte sensor | ||
Patent #
US 8,133,178 B2
Filed 02/22/2006
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Systems and methods for replacing signal artifacts in a glucose sensor data stream | ||
Patent #
US 8,150,488 B2
Filed 10/14/2009
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Device and method for determining analyte levels | ||
Patent #
US 8,155,723 B2
Filed 01/28/2010
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Calibration techniques for a continuous analyte sensor | ||
Patent #
US 8,160,671 B2
Filed 09/01/2010
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 8,162,829 B2
Filed 03/30/2009
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Systems and methods for replacing signal artifacts in a glucose sensor data stream | ||
Patent #
US 8,167,801 B2
Filed 03/25/2010
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 8,175,673 B2
Filed 11/09/2009
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 8,177,716 B2
Filed 12/21/2009
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Systems and methods for replacing signal artifacts in a glucose sensor data stream | ||
Patent #
US 8,195,265 B2
Filed 02/09/2011
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
System and methods for processing analyte sensor data | ||
Patent #
US 8,206,297 B2
Filed 12/16/2009
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Signal processing for continuous analyte sensor | ||
Patent #
US 8,216,139 B2
Filed 09/23/2009
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 8,224,413 B2
Filed 10/10/2008
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 8,226,558 B2
Filed 09/27/2010
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 8,226,557 B2
Filed 12/28/2009
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 8,226,555 B2
Filed 03/18/2009
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Systems and methods for replacing signal artifacts in a glucose sensor data stream | ||
Patent #
US 8,229,536 B2
Filed 05/27/2010
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte sensor | ||
Patent #
US 8,231,531 B2
Filed 06/01/2006
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 8,231,532 B2
Filed 04/30/2007
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Systems and methods for processing analyte sensor data | ||
Patent #
US 8,233,959 B2
Filed 09/01/2006
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Signal processing for continuous analyte sensor | ||
Patent #
US 8,233,958 B2
Filed 10/12/2009
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 8,235,896 B2
Filed 12/21/2009
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Calibration techniques for a continuous analyte sensor | ||
Patent #
US 8,249,684 B2
Filed 09/01/2010
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Signal processing for continuous analyte sensor | ||
Patent #
US 8,251,906 B2
Filed 04/15/2009
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Oxygen enhancing membrane systems for implantable devices | ||
Patent #
US 8,255,032 B2
Filed 01/15/2010
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Oxygen enhancing membrane systems for implantable devices | ||
Patent #
US 8,255,030 B2
Filed 04/25/2006
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 8,255,031 B2
Filed 03/17/2009
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Oxygen enhancing membrane systems for implantable devices | ||
Patent #
US 8,255,033 B2
Filed 04/25/2006
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Signal processing for continuous analyte sensor | ||
Patent #
US 8,257,259 B2
Filed 10/16/2008
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 8,260,392 B2
Filed 06/09/2008
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Systems and methods for replacing signal data artifacts in a glucose sensor data stream | ||
Patent #
US 8,260,393 B2
Filed 06/13/2007
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 8,265,726 B2
Filed 11/09/2009
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Signal processing for continuous analyte sensor | ||
Patent #
US 8,265,725 B2
Filed 10/12/2009
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 8,273,022 B2
Filed 02/13/2009
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 8,275,439 B2
Filed 11/09/2009
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Implantable analyte sensor | ||
Patent #
US 8,277,713 B2
Filed 05/03/2004
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Transcutaneous analyte sensor | ||
Patent #
US 8,280,475 B2
Filed 02/23/2009
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Integrated receiver for continuous analyte sensor | ||
Patent #
US 8,282,550 B2
Filed 07/29/2008
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Signal processing for continuous analyte sensor | ||
Patent #
US 8,282,549 B2
Filed 12/08/2004
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 8,287,454 B2
Filed 09/27/2010
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Analyte sensor | ||
Patent #
US 8,287,453 B2
Filed 11/07/2008
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Signal processing for continuous analyte sensor | ||
Patent #
US 8,290,561 B2
Filed 09/23/2009
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Systems and methods for replacing signal artifacts in a glucose sensor data stream | ||
Patent #
US 8,292,810 B2
Filed 01/27/2011
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 8,306,598 B2
Filed 11/09/2009
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Transcutaneous analyte sensor | ||
Patent #
US 8,311,749 B2
Filed 05/26/2011
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Transcutaneous analyte sensor | ||
Patent #
US 8,321,149 B2
Filed 06/29/2011
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 8,346,336 B2
Filed 03/18/2009
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 8,346,337 B2
Filed 06/30/2009
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
System and methods for replacing signal artifacts in a glucose sensor data stream | ||
Patent #
US 8,346,338 B2
Filed 01/27/2011
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 8,353,829 B2
Filed 12/21/2009
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 8,357,091 B2
Filed 12/21/2009
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 8,366,614 B2
Filed 03/30/2009
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Systems and methods for processing sensor data | ||
Patent #
US 8,369,919 B2
Filed 10/24/2008
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 8,372,005 B2
Filed 12/21/2009
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Signal processing for continuous analyte sensor | ||
Patent #
US 8,374,667 B2
Filed 10/16/2008
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 8,380,273 B2
Filed 04/11/2009
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Calibration techniques for a continuous analyte sensor | ||
Patent #
US 8,386,004 B2
Filed 09/07/2011
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 8,391,945 B2
Filed 03/17/2009
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
System and methods for processing analyte sensor data | ||
Patent #
US 8,394,021 B2
Filed 10/01/2007
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 8,409,131 B2
Filed 03/07/2007
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Systems and methods for replacing signal artifacts in a glucose sensor data stream | ||
Patent #
US 8,412,301 B2
Filed 02/09/2011
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Systems and methods for processing sensor data | ||
Patent #
US 8,423,113 B2
Filed 10/24/2008
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Dual electrode system for a continuous analyte sensor | ||
Patent #
US 8,423,114 B2
Filed 10/01/2007
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Calibration techniques for a continuous analyte sensor | ||
Patent #
US 8,428,678 B2
Filed 05/16/2012
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Systems and methods for replacing signal artifacts in a glucose sensor data stream | ||
Patent #
US 8,435,179 B2
Filed 01/27/2011
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
System and methods for processing analyte sensor data | ||
Patent #
US 8,442,610 B2
Filed 08/21/2008
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Transcutaneous analyte sensor | ||
Patent #
US 8,457,708 B2
Filed 12/05/2008
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Integrated delivery device for continuous glucose sensor | ||
Patent #
US 8,460,231 B2
Filed 07/11/2011
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 8,465,425 B2
Filed 06/30/2009
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Optical sensor configuration for ratiometric correction of blood glucose measurement | ||
Patent #
US 8,467,843 B2
Filed 11/04/2009
|
Current Assignee
Medtronic Minimed Incorporated
|
Original Assignee
GluMetrics Inc.
|
Signal processing for continuous analyte sensor | ||
Patent #
US 8,469,886 B2
Filed 09/23/2009
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 8,473,021 B2
Filed 07/31/2009
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 8,480,580 B2
Filed 04/19/2007
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Transcutaneous analyte sensor | ||
Patent #
US 8,483,791 B2
Filed 04/11/2008
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Systems and methods for replacing signal artifacts in a glucose sensor data stream | ||
Patent #
US 8,491,474 B2
Filed 01/27/2011
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Optical determination of pH and glucose | ||
Patent #
US 8,498,682 B2
Filed 07/02/2010
|
Current Assignee
Medtronic Minimed Incorporated
|
Original Assignee
GluMetrics Inc.
|
Sensor head for use with implantable devices | ||
Patent #
US 8,509,871 B2
Filed 10/28/2008
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Sensor for percutaneous intravascular deployment without an indwelling cannula | ||
Patent #
US 8,512,245 B2
Filed 04/16/2009
|
Current Assignee
Medtronic Minimed Incorporated
|
Original Assignee
GluMetrics Inc.
|
Transcutaneous analyte sensor | ||
Patent #
US 8,515,519 B2
Filed 02/26/2009
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Device and method for determining analyte levels | ||
Patent #
US 8,527,025 B1
Filed 11/22/1999
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Device and method for determining analyte levels | ||
Patent #
US 8,527,026 B2
Filed 03/02/2012
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Use of an equilibrium intravascular sensor to achieve tight glycemic control | ||
Patent #
US 8,535,262 B2
Filed 12/09/2011
|
Current Assignee
Medtronic Minimed Incorporated
|
Original Assignee
GluMetrics Inc.
|
System and methods for processing analyte sensor data | ||
Patent #
US 8,548,553 B2
Filed 06/22/2012
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Particle-containing membrane and particulate electrode for analyte sensors | ||
Patent #
US 8,560,039 B2
Filed 09/17/2009
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
System and methods for processing analyte sensor data for sensor calibration | ||
Patent #
US 8,560,037 B2
Filed 03/26/2010
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Transcutaneous analyte sensor | ||
Patent #
US 8,565,848 B2
Filed 05/07/2009
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Integrated medicament delivery device for use with continuous analyte sensor | ||
Patent #
US 8,562,558 B2
Filed 06/05/2008
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
System and methods for processing analyte sensor data for sensor calibration | ||
Patent #
US 8,579,816 B2
Filed 01/07/2010
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Polymer membranes for continuous analyte sensors | ||
Patent #
US 8,583,204 B2
Filed 03/05/2010
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 8,597,189 B2
Filed 03/03/2009
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 8,612,159 B2
Filed 02/16/2004
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Analyte sensor | ||
Patent #
US 8,615,282 B2
Filed 02/22/2006
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
System and methods for processing analyte sensor data for sensor calibration | ||
Patent #
US 8,611,978 B2
Filed 01/07/2010
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 8,617,071 B2
Filed 06/21/2007
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
System and methods for processing analyte sensor data | ||
Patent #
US 8,622,905 B2
Filed 12/11/2009
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 8,622,906 B2
Filed 12/21/2009
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 8,641,619 B2
Filed 12/21/2009
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 8,649,841 B2
Filed 04/03/2007
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 8,652,043 B2
Filed 07/20/2012
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Signal processing for continuous analyte sensor | ||
Patent #
US 8,657,745 B2
Filed 10/16/2008
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Systems and methods for processing analyte sensor data | ||
Patent #
US 8,657,747 B2
Filed 04/05/2011
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 8,660,627 B2
Filed 03/17/2009
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Transcutaneous analyte sensor | ||
Patent #
US 8,663,109 B2
Filed 03/29/2010
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 8,666,469 B2
Filed 11/16/2007
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 8,668,645 B2
Filed 01/03/2003
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 8,670,815 B2
Filed 04/30/2007
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 8,672,844 B2
Filed 02/27/2004
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Systems and methods for processing analyte sensor data | ||
Patent #
US 8,672,845 B2
Filed 03/25/2010
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
System and methods for processing analyte sensor data | ||
Patent #
US 8,676,287 B2
Filed 12/11/2009
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Device and method for determining analyte levels | ||
Patent #
US 8,676,288 B2
Filed 06/22/2011
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Polymer membranes for continuous analyte sensors | ||
Patent #
US 8,682,408 B2
Filed 03/05/2010
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 8,688,188 B2
Filed 06/30/2009
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Transcutaneous analyte sensor | ||
Patent #
US 8,690,775 B2
Filed 04/11/2008
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Optical sensor configuration for ratiometric correction of glucose measurement | ||
Patent #
US 8,700,115 B2
Filed 05/15/2013
|
Current Assignee
Medtronic Minimed Incorporated
|
Original Assignee
GluMetrics Inc.
|
System and methods for processing analyte sensor data | ||
Patent #
US 8,700,117 B2
Filed 12/08/2009
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Sensors with thromboresistant coating | ||
Patent #
US 8,715,589 B2
Filed 05/14/2013
|
Current Assignee
Medtronic Minimed Incorporated
|
Original Assignee
Medtronic Minimed Incorporated
|
Transcutaneous analyte sensor | ||
Patent #
US 8,721,545 B2
Filed 03/22/2010
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 8,734,348 B2
Filed 03/17/2009
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 8,734,346 B2
Filed 04/30/2007
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Equilibrium non-consuming fluorescence sensor for real time intravascular glucose measurement | ||
Patent #
US 8,738,107 B2
Filed 05/09/2008
|
Current Assignee
Medtronic Minimed Incorporated
|
Original Assignee
Medtronic Minimed Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 8,738,109 B2
Filed 03/03/2009
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Cellulosic-based resistance domain for an analyte sensor | ||
Patent #
US 8,744,546 B2
Filed 04/28/2006
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 8,744,545 B2
Filed 03/03/2009
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Signal processing for continuous analyte sensor | ||
Patent #
US 8,747,315 B2
Filed 09/23/2009
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte sensor | ||
Patent #
US 8,750,955 B2
Filed 11/02/2009
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
System and methods for processing analyte sensor data | ||
Patent #
US 8,761,856 B2
Filed 04/27/2012
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
System and methods for processing analyte sensor data | ||
Patent #
US 8,771,187 B2
Filed 05/31/2011
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
System and methods for processing analyte sensor data | ||
Patent #
US 8,774,888 B2
Filed 01/20/2010
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 8,774,887 B2
Filed 03/24/2007
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Systems and methods for replacing signal artifacts in a glucose sensor data stream | ||
Patent #
US 8,777,853 B2
Filed 04/04/2012
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
System and methods for processing analyte sensor data | ||
Patent #
US 8,788,006 B2
Filed 12/11/2009
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
System and methods for processing analyte sensor data | ||
Patent #
US 8,788,008 B2
Filed 05/31/2011
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Systems and methods for replacing signal artifacts in a glucose sensor data stream | ||
Patent #
US 8,790,260 B2
Filed 10/14/2009
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Transcutaneous analyte sensor | ||
Patent #
US 8,792,954 B2
Filed 03/19/2010
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Transcutaneous analyte sensor | ||
Patent #
US 8,792,955 B2
Filed 06/09/2011
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Transcutaneous analyte sensor | ||
Patent #
US 8,792,953 B2
Filed 03/19/2010
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Systems and methods for replacing signal artifacts in a glucose sensor data stream | ||
Patent #
US 8,795,177 B2
Filed 01/14/2009
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Transcutaneous analyte sensor | ||
Patent #
US 8,801,611 B2
Filed 03/22/2010
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
System and methods for processing analyte sensor data | ||
Patent #
US 8,801,612 B2
Filed 04/27/2012
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Signal processing for continuous analyte sensor | ||
Patent #
US 8,801,610 B2
Filed 07/24/2009
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Integrated medicament delivery device for use with continuous analyte sensor | ||
Patent #
US 8,808,228 B2
Filed 06/05/2008
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
System and methods for processing analyte sensor data | ||
Patent #
US 8,808,182 B2
Filed 04/27/2012
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Transcutaneous medical device with variable stiffness | ||
Patent #
US 8,812,072 B2
Filed 04/17/2008
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Systems and methods for replacing signal artifacts in a glucose sensor data stream | ||
Patent #
US 8,812,073 B2
Filed 06/01/2010
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Systems and methods for replacing signal artifacts in a glucose sensor data stream | ||
Patent #
US 8,821,400 B2
Filed 02/09/2011
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Optical systems and methods for ratiometric measurement of blood glucose concentration | ||
Patent #
US 8,838,195 B2
Filed 02/06/2008
|
Current Assignee
Medtronic Minimed Incorporated
|
Original Assignee
Medtronic Minimed Incorporated
|
Membrane for use with implantable devices | ||
Patent #
US 8,840,552 B2
Filed 12/08/2009
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 8,840,553 B2
Filed 02/26/2009
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Systems and methods for replacing signal artifacts in a glucose sensor data stream | ||
Patent #
US 8,843,187 B2
Filed 06/01/2010
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 8,880,137 B2
Filed 04/18/2003
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Integrated delivery device for continuous glucose sensor | ||
Patent #
US 8,882,741 B2
Filed 04/30/2012
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte sensor | ||
Patent #
US 8,886,273 B2
Filed 11/07/2008
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte sensor | ||
Patent #
US 8,886,272 B2
Filed 02/22/2006
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Oxygen enhancing membrane systems for implantable devices | ||
Patent #
US 8,909,314 B2
Filed 07/20/2011
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Dual electrode system for a continuous analyte sensor | ||
Patent #
US 8,911,369 B2
Filed 12/15/2008
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Transcutaneous analyte sensor | ||
Patent #
US 8,915,849 B2
Filed 02/03/2009
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 8,915,850 B2
Filed 03/28/2014
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 8,920,319 B2
Filed 12/28/2012
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Integrated delivery device for continuous glucose sensor | ||
Patent #
US 8,920,401 B2
Filed 04/30/2012
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Device and method for determining analyte levels | ||
Patent #
US 8,923,947 B2
Filed 07/23/2013
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Polymer membranes for continuous analyte sensors | ||
Patent #
US 8,954,128 B2
Filed 10/18/2013
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 8,974,386 B2
Filed 11/01/2005
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Use of an equilibrium sensor to monitor glucose concentration | ||
Patent #
US 8,979,790 B2
Filed 09/11/2013
|
Current Assignee
Medtronic Minimed Incorporated
|
Original Assignee
Medtronic Minimed Incorporated
|
Optical determination of pH and glucose | ||
Patent #
US 8,983,565 B2
Filed 07/25/2013
|
Current Assignee
Medtronic Minimed Incorporated
|
Original Assignee
Medtronic Minimed Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 9,011,332 B2
Filed 10/30/2007
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 9,011,331 B2
Filed 12/29/2004
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 9,014,773 B2
Filed 03/07/2007
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 9,042,953 B2
Filed 03/02/2007
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Transcutaneous analyte sensor | ||
Patent #
US 9,044,199 B2
Filed 03/10/2005
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Integrated delivery device for continuous glucose sensor | ||
Patent #
US 9,050,413 B2
Filed 04/30/2012
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Transcutaneous analyte sensor | ||
Patent #
US 9,055,901 B2
Filed 09/14/2012
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Transcutaneous analyte sensor | ||
Patent #
US 9,060,742 B2
Filed 03/19/2010
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 9,066,695 B2
Filed 04/12/2007
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 9,066,697 B2
Filed 10/27/2011
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 9,066,694 B2
Filed 04/03/2007
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 9,072,477 B2
Filed 06/21/2007
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Transcutaneous analyte sensor | ||
Patent #
US 9,078,626 B2
Filed 03/31/2011
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 9,078,607 B2
Filed 06/17/2013
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
System and methods for processing analyte sensor data for sensor calibration | ||
Patent #
US 9,078,608 B2
Filed 07/13/2012
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Signal processing for continuous analyte sensor | ||
Patent #
US 9,107,623 B2
Filed 04/15/2009
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Systems and methods for replacing signal artifacts in a glucose sensor data stream | ||
Patent #
US 9,149,219 B2
Filed 02/09/2011
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Low oxygen in vivo analyte sensor | ||
Patent #
US 9,155,496 B2
Filed 02/18/2011
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Integrated delivery device for continuous glucose sensor | ||
Patent #
US 9,155,843 B2
Filed 07/26/2012
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Polymer membranes for continuous analyte sensors | ||
Patent #
US 9,173,607 B2
Filed 01/30/2014
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Polymer membranes for continuous analyte sensors | ||
Patent #
US 9,173,606 B2
Filed 01/30/2014
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Signal processing for continuous analyte sensor | ||
Patent #
US 9,192,328 B2
Filed 09/23/2009
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
System and methods for processing analyte sensor data for sensor calibration | ||
Patent #
US 9,220,449 B2
Filed 07/09/2013
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte sensor | ||
Patent #
US 9,247,900 B2
Filed 06/04/2013
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Systems and methods for replacing signal artifacts in a glucose sensor data stream | ||
Patent #
US 9,247,901 B2
Filed 08/02/2006
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Systems and methods for replacing signal artifacts in a glucose sensor data stream | ||
Patent #
US 9,282,925 B2
Filed 03/25/2010
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
System and methods for processing analyte sensor data for sensor calibration | ||
Patent #
US 9,314,196 B2
Filed 09/07/2012
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 9,326,716 B2
Filed 12/05/2014
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Sensor head for use with implantable devices | ||
Patent #
US 9,328,371 B2
Filed 07/16/2013
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 9,326,714 B2
Filed 06/29/2010
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Device and method for determining analyte levels | ||
Patent #
US 9,339,223 B2
Filed 12/30/2013
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Particle-containing membrane and particulate electrode for analyte sensors | ||
Patent #
US 9,339,222 B2
Filed 05/31/2013
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Signal processing for continuous analyte sensor | ||
Patent #
US 9,351,668 B2
Filed 10/12/2009
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Signal processing for continuous analyte sensor | ||
Patent #
US 9,364,173 B2
Filed 09/23/2009
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Transcutaneous analyte sensor | ||
Patent #
US 9,414,777 B2
Filed 03/10/2005
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Signal processing for continuous analyte sensor | ||
Patent #
US 9,420,965 B2
Filed 07/01/2011
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Systems and methods for replacing signal artifacts in a glucose sensor data stream | ||
Patent #
US 9,420,968 B2
Filed 04/04/2012
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Systems and methods for replacing signal artifacts in a glucose sensor data stream | ||
Patent #
US 9,427,183 B2
Filed 07/12/2011
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Device and method for determining analyte levels | ||
Patent #
US 9,439,589 B2
Filed 11/25/2014
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Methods and systems for promoting glucose management | ||
Patent #
US 9,446,194 B2
Filed 03/26/2010
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte sensor | ||
Patent #
US 9,451,908 B2
Filed 12/19/2012
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 9,498,159 B2
Filed 10/30/2007
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Signal processing for continuous analyte sensor | ||
Patent #
US 9,498,155 B2
Filed 10/16/2008
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Dual electrode system for a continuous analyte sensor | ||
Patent #
US 9,504,413 B2
Filed 04/15/2013
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Systems and methods for replacing signal artifacts in a glucose sensor data stream | ||
Patent #
US 9,510,782 B2
Filed 04/04/2012
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Membrane for use with implantable devices | ||
Patent #
US 9,532,741 B2
Filed 07/25/2014
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Integrated receiver for continuous analyte sensor | ||
Patent #
US 9,538,946 B2
Filed 03/25/2010
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Polymer membranes for continuous analyte sensors | ||
Patent #
US 9,549,699 B2
Filed 10/17/2014
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Polymer membranes for continuous analyte sensors | ||
Patent #
US 9,566,026 B2
Filed 10/17/2014
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Polymer membranes for continuous analyte sensors | ||
Patent #
US 9,572,523 B2
Filed 09/22/2015
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Dual electrode system for a continuous analyte sensor | ||
Patent #
US 9,579,053 B2
Filed 03/26/2010
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Systems and methods for replacing signal artifacts in a glucose sensor data stream | ||
Patent #
US 9,585,607 B2
Filed 04/04/2012
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Oxygen enhancing membrane systems for implantable devices | ||
Patent #
US 9,597,027 B2
Filed 10/30/2014
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 9,610,034 B2
Filed 11/09/2015
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Transcutaneous analyte sensor | ||
Patent #
US 9,610,031 B2
Filed 04/13/2011
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Systems and methods for replacing signal artifacts in a glucose sensor data stream | ||
Patent #
US 9,649,069 B2
Filed 06/29/2016
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte sensor | ||
Patent #
US 9,668,677 B2
Filed 10/26/2015
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Polymer membranes for continuous analyte sensors | ||
Patent #
US 9,693,721 B2
Filed 06/17/2015
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Systems and methods for processing sensor data | ||
Patent #
US 9,717,449 B2
Filed 01/15/2013
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte sensor | ||
Patent #
US 9,724,028 B2
Filed 11/24/2014
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Systems and methods for replacing signal artifacts in a glucose sensor data stream | ||
Patent #
US 9,724,045 B1
Filed 04/06/2017
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Integrated medicament delivery device for use with continuous analyte sensor | ||
Patent #
US 9,741,139 B2
Filed 08/09/2013
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Signal processing for continuous analyte sensor | ||
Patent #
US 9,750,441 B2
Filed 08/15/2016
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Systems and methods for replacing signal artifacts in a glucose sensor data stream | ||
Patent #
US 9,750,460 B2
Filed 04/14/2017
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Low oxygen in vivo analyte sensor | ||
Patent #
US 9,757,061 B2
Filed 09/01/2015
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Transcutaneous analyte sensor | ||
Patent #
US 9,775,543 B2
Filed 12/30/2013
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte sensing biointerface | ||
Patent #
US 9,788,766 B2
Filed 05/19/2014
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Transcutaneous analyte sensor | ||
Patent #
US 9,801,572 B2
Filed 06/18/2015
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Sensor head for use with implantable devices | ||
Patent #
US 9,804,114 B2
Filed 03/02/2016
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Transcutaneous analyte sensor | ||
Patent #
US 9,814,414 B2
Filed 03/30/2010
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Transcutaneous analyte sensor | ||
Patent #
US 9,833,143 B2
Filed 06/05/2014
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Optical systems and methods for ratiometric measurement of blood glucose concentration | ||
Patent #
US 9,839,378 B2
Filed 08/07/2014
|
Current Assignee
Medtronic Minimed Incorporated
|
Original Assignee
Medtronic Minimed Incorporated
|
System and methods for processing analyte sensor data | ||
Patent #
US 9,895,089 B2
Filed 05/20/2014
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
System and methods for processing analyte sensor data for sensor calibration | ||
Patent #
US 9,918,668 B2
Filed 03/09/2016
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Device and method for determining analyte levels | ||
Patent #
US 9,931,067 B2
Filed 09/13/2016
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Integrated delivery device for continuous glucose sensor | ||
Patent #
US 9,937,293 B2
Filed 08/19/2015
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte sensor | ||
Patent #
US 9,986,942 B2
Filed 08/10/2006
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Oxygen enhancing membrane systems for implantable devices | ||
Patent #
US 9,993,186 B2
Filed 02/09/2017
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte sensor | ||
Patent #
US 10,022,078 B2
Filed 05/23/2006
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Particle-containing membrane and particulate electrode for analyte sensors | ||
Patent #
US 10,028,683 B2
Filed 10/07/2014
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Particle-containing membrane and particulate electrode for analyte sensors | ||
Patent #
US 10,028,684 B2
Filed 09/21/2017
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Membrane for use with implantable devices | ||
Patent #
US 10,039,480 B2
Filed 02/11/2015
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Dual electrode system for a continuous analyte sensor | ||
Patent #
US 10,136,844 B2
Filed 11/18/2016
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Polymer membranes for continuous analyte sensors | ||
Patent #
US 10,143,410 B2
Filed 06/01/2017
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Systems and methods for processing sensor data | ||
Patent #
US 10,182,751 B2
Filed 06/26/2017
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 10,201,301 B2
Filed 04/18/2016
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 10,231,654 B2
Filed 06/23/2015
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Low oxygen in vivo analyte sensor | ||
Patent #
US 10,265,000 B2
Filed 08/03/2017
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Integrated medicament delivery device for use with continuous analyte sensor | ||
Patent #
US 10,278,580 B2
Filed 06/09/2014
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Dual electrode system for a continuous analyte sensor | ||
Patent #
US 10,299,712 B2
Filed 09/05/2017
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Cellulosic-based resistance domain for an analyte sensor | ||
Patent #
US 10,300,507 B2
Filed 02/14/2014
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte sensor | ||
Patent #
US 10,314,525 B2
Filed 01/06/2015
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Transcutaneous analyte sensor | ||
Patent #
US 10,327,638 B2
Filed 10/30/2017
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte sensor | ||
Patent #
US 10,349,873 B2
Filed 04/27/2016
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte sensing biointerface | ||
Patent #
US 10,376,188 B2
Filed 09/21/2017
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Integrated medicament delivery device for use with continuous analyte sensor | ||
Patent #
US 10,403,012 B2
Filed 07/18/2017
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte monitoring device and methods of use | ||
Patent #
US 10,478,108 B2
Filed 02/05/2016
|
Current Assignee
Abbott Diabetes Care Incorporated
|
Original Assignee
Abbott Diabetes Care Incorporated
|
Transcutaneous analyte sensor | ||
Patent #
US 10,524,703 B2
Filed 01/24/2014
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Methods and systems for promoting glucose management | ||
Patent #
US 10,537,678 B2
Filed 12/16/2015
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Particle-containing membrane and particulate electrode for analyte sensors | ||
Patent #
US 10,561,352 B2
Filed 07/03/2018
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
System and methods for processing analyte sensor data for sensor calibration | ||
Patent #
US 10,610,137 B2
Filed 06/28/2019
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
System and methods for processing analyte sensor data for sensor calibration | ||
Patent #
US 10,610,136 B2
Filed 06/28/2019
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Oxygen enhancing membrane systems for implantable devices | ||
Patent #
US 10,610,140 B2
Filed 05/11/2018
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
System and methods for processing analyte sensor data for sensor calibration | ||
Patent #
US 10,610,135 B2
Filed 06/28/2019
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Methods and systems for promoting glucose management | ||
Patent #
US 10,610,642 B2
Filed 12/30/2013
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
System and methods for processing analyte sensor data for sensor calibration | ||
Patent #
US 10,617,336 B2
Filed 06/28/2019
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Integrated insulin delivery system with continuous glucose sensor | ||
Patent #
US 10,653,835 B2
Filed 10/24/2017
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte sensing biointerface | ||
Patent #
US 10,667,729 B2
Filed 06/27/2019
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte sensing biointerface | ||
Patent #
US 10,667,730 B2
Filed 10/16/2019
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Methods and systems for simulating glucose response to simulated actions | ||
Patent #
US 10,675,405 B2
Filed 12/04/2015
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte sensing biointerface | ||
Patent #
US 10,702,193 B2
Filed 01/14/2020
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
System and methods for processing analyte sensor data for sensor calibration | ||
Patent #
US 10,709,364 B2
Filed 11/21/2019
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte sensor | ||
Patent #
US 10,709,362 B2
Filed 11/21/2019
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte sensor | ||
Patent #
US 10,709,363 B2
Filed 11/21/2019
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
System and methods for processing analyte sensor data for sensor calibration | ||
Patent #
US 10,716,498 B2
Filed 11/21/2019
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte sensor | ||
Patent #
US 10,722,152 B2
Filed 11/05/2019
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
System and methods for processing analyte sensor data for sensor calibration | ||
Patent #
US 10,743,801 B2
Filed 11/21/2019
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
System and methods for processing analyte sensor data | ||
Patent #
US 10,786,185 B2
Filed 01/05/2018
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte sensor | ||
Patent #
US 10,799,158 B2
Filed 11/21/2019
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte sensor | ||
Patent #
US 10,799,159 B2
Filed 02/13/2020
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte sensor | ||
Patent #
US 10,813,577 B2
Filed 02/13/2020
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Analyte sensor | ||
Patent #
US 10,813,576 B2
Filed 11/21/2019
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Integrated insulin delivery system with continuous glucose sensor | ||
Patent #
US 10,835,672 B2
Filed 05/05/2020
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
System and methods for processing analyte sensor data for sensor calibration | ||
Patent #
US 10,856,787 B2
Filed 07/31/2019
|
Current Assignee
DexCom Incorporated
|
Original Assignee
DexCom Incorporated
|
Long wave fluorophore sensor compounds and other fluorescent sensor compounds in polymers | ||
Patent #
US 6,766,183 B2
Filed 12/28/2001
|
Current Assignee
Regents of the University of California, Lawrence Livermore National Security LLC
|
Original Assignee
Medtronic Minimed Incorporated, Regents of the University of California
|
Optical determination of glucose utilizing boronic acid adducts | ||
Patent #
US 20060083688A1
Filed 12/07/2005
|
Current Assignee
Regents of the University of California
|
Original Assignee
Regents of the University of California
|
Optical determination of glucose utilizing boronic acid adducts | ||
Patent #
US 20040028612A1
Filed 06/05/2003
|
Current Assignee
Regents of the University of California
|
Original Assignee
Regents of the University of California
|
Detection of analytes in aqueous environments | ||
Patent #
US 6,794,195 B2
Filed 08/03/2001
|
Current Assignee
Senseonics Incorporated
|
Original Assignee
Sensors For Medicine and Science Incorporated
|
Detection of biological molecules using chemical amplification and optical sensors | ||
Patent #
US 6,804,544 B2
Filed 08/21/2001
|
Current Assignee
Minimed Inc.
|
Original Assignee
Minimed Inc.
|
Detection of glucose in solutions also containing an alpha-hydroxy acid or a beta-diketone | ||
Patent #
US 6,800,451 B2
Filed 07/03/2002
|
Current Assignee
Sensors For Medicine and Science Incorporated
|
Original Assignee
Sensors For Medicine and Science Incorporated
|
Polyhydroxyl-substituted organic molecule sensing optical in vivo method utilizing a boronic acid adduct and the device thereof | ||
Patent #
US 6,627,177 B2
Filed 12/05/2000
|
Current Assignee
Regents of the University of California
|
Original Assignee
Regents of the University of California
|
Polyhydroxyl-substituted organic molecule sensing method and device | ||
Patent #
US 6,653,141 B2
Filed 12/05/2000
|
Current Assignee
Regents of the University of California
|
Original Assignee
Regents of the University of California
|
Detection of biological molecules using chemical amplification and optical sensors | ||
Patent #
US 6,319,540 B1
Filed 09/22/1999
|
Current Assignee
Minimed Inc.
|
Original Assignee
Minimed Inc.
|
Detection of biological molecules using boronate-based chemical amplification and optical sensors | ||
Patent #
US 6,002,954 A
Filed 11/21/1996
|
Current Assignee
Regents of the University of California, Lawrence Livermore National Security LLC
|
Original Assignee
Minimed Inc., Regents of the University of California
|
Boronic acid compound having a binaphthyl group | ||
Patent #
US 5,763,238 A
Filed 12/28/1995
|
Current Assignee
Research Development Corporation Of Japan
|
Original Assignee
Research Development Corporation Of Japan
|
Fluorescent compound suitable for use in the detection of saccharides | ||
Patent #
US 5,503,770 A
Filed 11/07/1994
|
Current Assignee
Research Development Corporation Of Japan
|
Original Assignee
Research Development Corporation Of Japan
|
Method and means for detecting polyhydroxyl compounds | ||
Patent #
US 5,512,246 A
Filed 11/17/1993
|
Current Assignee
Medtronic Minimed Incorporated
|
Original Assignee
Anthony P. Russell
|
Method for detecting polyhydroxyl compounds | ||
Patent #
US 5,137,833 A
Filed 09/21/1989
|
Current Assignee
Medtronic Minimed Incorporated
|
Original Assignee
Anthony P. Russell
|
7 Claims
- 1. The compound:
1 Specification
This application is a continuation of U.S. application Ser. No. 11/782,553, filed Jul. 24, 2007, which claims the benefit of U.S. Provisional Application No. 60/833,081 filed Jul. 25, 2006, both of which are hereby incorporated by reference in their entireties.
1. Field of the Invention
Novel fluorescent dyes are disclosed for use in analyte detection.
2. Description of the Related Art
Fluorescent dyes, including 8-hydroxypyrene-1,3,6-trisulfonic acid (HPTS) and its derivatives, are known and have been used in analyte detection. See e.g., U.S. Pat. Nos. 6,653,141, 6,627,177, 5,512,246, 5,137,833, 6,800,451, 6,794,195, 6,804,544, 6,002,954, 6,319,540, 6,766,183, 5,503,770, and 5,763,238; and co-pending U.S. patent application Ser. Nos. 10/456,895 and 11/296,898; each of which is incorporated herein in its entirety by reference thereto.
Fluorescent dyes having the below generic structure are disclosed in accordance with embodiments of the present invention.
wherein:
R3 is —(CH2)n-A−M+,
- wherein n is 1-4,
- wherein A− is an anionic group selected from the group consisting of SO3−, HPO3−, CO2− and
-
- wherein M+ is a cationic group selected from the group consisting of H+, an alkali metal ion, Li+, Na+, K+, Rb+, Cs+, Fr+, an onium ion and NR4+, wherein R is selected from the group consisting of alkyl, alkylaryl and aromatic groups);
R5 is selected from the group consisting of
-
- wherein n is equal to 1-10, n′ is equal to 2-4, and Y is selected from the group consisting of NH and O;
R6 is selected from the group consisting of NHR7, OR7 and CO2H; and
R7 is H or an ethylenically unsaturated group selected from the group consisting of methacryloyl, acryloyl, styryl, acrylamido and methacrylamido.
- wherein n is equal to 1-10, n′ is equal to 2-4, and Y is selected from the group consisting of NH and O;
Fluorescent dyes having the below generic structure are disclosed in accordance with preferred embodiments of the present invention.
wherein:
R3 is —(CH2)n-A−M+,
- wherein n is 1-4,
- wherein A− is an anionic group selected from the group consisting of SO3−, HPO3−, CO2− and
-
- wherein M+ is a cationic group selected from the group consisting of H+, an alkali metal ion, Li+, Na+, K+, Rb+, Cs+, Fr+, an onium ion and NR4+, wherein R is selected from the group consisting of alkyl, alkylaryl and aromatic groups);
R8 is selected from the group consisting of
- wherein M+ is a cationic group selected from the group consisting of H+, an alkali metal ion, Li+, Na+, K+, Rb+, Cs+, Fr+, an onium ion and NR4+, wherein R is selected from the group consisting of alkyl, alkylaryl and aromatic groups);
-
- wherein n is equal to 1-10, n′ is equal to 2-4;
R9 is selected from the group consisting of NHR10, OR10 and CO2H; and
R10 is H or an ethylenically unsaturated group selected from the group consisting of methacryloyl, acryloyl, styryl, acrylamido and methacrylamido.
- wherein n is equal to 1-10, n′ is equal to 2-4;
A fluorescent dye termed HPTS-Cys-MA (or HPTS-TriCys-MA) having the below structure is disclosed in accordance with preferred embodiments of the present invention.
A glucose sensor is disclosed in accordance with another embodiment of the present invention, comprising the dyes disclosed herein (e.g., HPTS-Cys-MA) and a quencher comprising boronic acid, such as 3,3′-oBBV.
A first method of making the generic class of compounds to which HPTS-Cys-MA belongs is disclosed in accordance with another embodiment of the present invention. The method comprises the following steps:
wherein:
R3 is —(CH2)n-A−M+,
- wherein n is 1-4,
- wherein A− is an anionic group selected from the group consisting of SO3−, HPO3−, CO2− and
-
- wherein M+ is a cationic group selected from the group consisting of H+, an alkali metal ion, Li+, Na+, K+, Rb+, Cs+, Fr+, an onium ion and NR4+, wherein R is selected from the group consisting of alkyl, alkylaryl and aromatic groups);
R5 is selected from the group consisting of
-
- wherein n is equal to 1-10, n′ is equal to 2-4 and Y is selected from the group consisting of NH and O;
R6 is selected from the group consisting of NHR7, OR7 and CO2H;
R7 is H or an ethylenically unsaturated group selected from the group consisting of methacryloyl, acryloyl, styryl acrylamide and methacrylamido; and
Z is an amino protecting group selected from the group consisting of phthalimido, Boc and Fmoc).
- wherein n is equal to 1-10, n′ is equal to 2-4 and Y is selected from the group consisting of NH and O;
A second method of making the generic class of compounds to which HPTS-Cys-MA belongs is disclosed in accordance with another embodiment of the present invention. The method comprises the steps of:
wherein:
R3 is —(CH2)n-A−M+,
- wherein n is 1-4,
- wherein A− is an anionic group selected from the group consisting of SO3−, HPO3−, CO2− and
-
- wherein M+ is a cationic group selected from the group consisting of H+, an alkali metal ion, Li+, Na+, K+, Rb+, Cs+, Fr+, an onium ion and NR4+, wherein R is selected from the group consisting of alkyl, alkylaryl and aromatic groups);
R8 is selected from the group consisting of
- wherein M+ is a cationic group selected from the group consisting of H+, an alkali metal ion, Li+, Na+, K+, Rb+, Cs+, Fr+, an onium ion and NR4+, wherein R is selected from the group consisting of alkyl, alkylaryl and aromatic groups);
-
- wherein n is equal to 1-10, n′ is equal to 2-4;
R9 is selected from the group consisting of NHR10, OR10 and CO2H; and
R10 is H or an ethylenically unsaturated group selected from the group consisting of methacryloyl, acryloyl, styryl acrylamide and methacrylamido.
- wherein n is equal to 1-10, n′ is equal to 2-4;
A specific method for making HPTS-Cys-MA is disclosed in accordance with another embodiment of the present invention. The method comprises the steps of making HPTS-CysOH as follows:
and making HPTS-Cys-MA as follows:
Another specific method for making HPTS-Cys-MA is disclosed in accordance with another embodiment of the present invention. The method comprises the steps of making:
a) TBCys as follows:
b) Phth acid as follows:
c) Phth MA as follows:
d) AminoCysMA as follows:
e) HPTS-Cys-MA as follows:
The fluorescent dyes of the invention are derivatives of 8-hydroxypyrene-1,3,6-trisulfonate (HPTS). The counterions can be H+ or any other cation. HPTS exhibits two excitation wavelengths at around 405 nm and around 450 nm, which correspond to the absorption wavelengths of the acid and its conjugate base, respectively. The shift in excitation wavelength is due to the pH-dependent ionization of the hydroxyl group on HPTS. As the pH increases, HPTS shows an increase in absorbance at about 450 nm, and a decrease in absorbance below about 420 nm. The pH-dependent shift in the absorption maximum enables dual-excitation ratiometric detection in the physiological range. The dyes may be used with a quencher comprising boronic acid, such as 3,3′-oBBV.
A generic structure of dyes in accordance with preferred embodiments of the present invention is:
wherein:
R3 is —(CH2)n-A−M+,
- wherein n is 1-4,
- wherein A− is an anionic group selected from the group consisting of SO3−, HPO3−, CO2− and
-
- wherein M+ is a cationic group selected from the group consisting of H+, an alkali metal ion, Li+, Na+, K+, Rb+, Cs+, Fr+, an onium ion and NR4+, wherein R is selected from the group consisting of alkyl, alkylaryl and aromatic groups);
R5 is selected from the group consisting of
-
- wherein n is equal to 1-10, n′ is equal to 2-4 and Y is selected from the group consisting of NH and O;
R6 is selected from the group consisting of NHR7, OR7 and CO2H; and
R7 is H or an ethylenically unsaturated group selected from the group consisting of methacryloyl, acryloyl, styryl acrylamide and methacrylamido.
- wherein n is equal to 1-10, n′ is equal to 2-4 and Y is selected from the group consisting of NH and O;
Another generic structure of dyes in accordance with preferred embodiments of the present invention is:
where:
R3 is —(CH2)n-A−M+,
- wherein n is 1-4,
- wherein A− is an anionic group selected from the group consisting of SO3−, HPO3−, CO2− and
-
- wherein M+ is a cationic group selected from the group consisting of H+, an alkali metal ion, Li+, Na+, K+, Rb+, Cs+, Fr+, an onium ion and NR4+, wherein R is selected from the group consisting of alkyl, alkylaryl and aromatic groups);
R8 is selected from the group consisting of
-
- wherein n is equal to 1-10, n′ is equal to 2-4;
R9 is selected from the group consisting of NHR10, OR10 and CO2H; and
R10 is H or an ethylenically unsaturated group selected from the group consisting of methacryloyl, acryloyl, styryl, acrylamido and methacrylamido.
- wherein n is equal to 1-10, n′ is equal to 2-4;
The structure of HPTS-Cys-MA is as follows:
As indicated in the generic structures above, substitutions other than CysMA on the HPTS core are consistent with aspects of the present invention, as long as the substitutions are negatively charged and have a polymerizable group. For example, either L or D stereoisomers of cysteic acid may be used. In some embodiments, only one or two of the sulfonic acids may be substituted. Likewise, in variations to HPTS-CysMA shown above, other counterions besides NBu4+ may be used, including positively charged metals, e.g., Na+. In other variations, the sulfonic acid groups may be replaced with e.g., phosphoric, carboxylic, etc. functional groups.
For comparison, the structure of HPTS-LysMA is pictured below as follows:
First Method of Making the Generic Class of Compounds to which HPTS-Cys-MA Belongs
A first method of making the generic class of compounds to which HPTS-Cys-MA belongs is disclosed in accordance with another embodiment of the present invention. The method comprises the following steps:
wherein:
R3 is —(CH2)n-A−M+,
- wherein n is 1-4,
- wherein A− is an anionic group selected from the group consisting of SO3−, HPO3−, CO2− and
-
- wherein M+ is a cationic group selected from the group consisting of H+, an alkali metal ion, Li+, Na+, K+, Rb+, Cs+, Fr+, an onium ion and NR4+, wherein R is selected from the group consisting of alkyl, alkylaryl and aromatic groups);
R5 is selected from the group consisting of
-
- wherein n is equal to 1-10, n′ is equal to 2-4 and Y is selected from the group consisting of NH and O;
R6 is selected from the group consisting of NHR7, OR7 and CO2H;
R7 is H or an ethylenically unsaturated group selected from the group consisting of methacryloyl, acryloyl, styryl, acrylamide and methacrylamido; and
Z is an amino protecting group selected from the group consisting of phthalimido, Boc and Fmoc).
Second Method of Making the Generic Class of Compounds to which HPTS-Cys-MA Belongs
- wherein n is equal to 1-10, n′ is equal to 2-4 and Y is selected from the group consisting of NH and O;
A second method of making the generic class of compounds to which HPTS-Cys-MA belongs is disclosed in accordance with another embodiment of the present invention. The method comprises the steps of:
wherein:
R3 is —(CH2)n-A−M+,
- wherein n is 1-4,
- wherein A− is an anionic group selected from the group consisting of SO3−, HPO3−, CO2− and
-
- wherein M+ is a cationic group selected from the group consisting of H+, an alkali metal ion, Li+, Na+, K+, Rb+, Cs+, Fr+, an onium ion and NR4+, wherein R is selected from the group consisting of alkyl, alkylaryl and aromatic groups);
R8 is selected from the group consisting of
- wherein M+ is a cationic group selected from the group consisting of H+, an alkali metal ion, Li+, Na+, K+, Rb+, Cs+, Fr+, an onium ion and NR4+, wherein R is selected from the group consisting of alkyl, alkylaryl and aromatic groups);
-
- wherein n is equal to 1-10, n′ is equal to 2-4;
R9 is selected from the group consisting of NHR10, OR10 and CO2H; and
R10 is H or an ethylenically unsaturated group selected from the group consisting of methacryloyl, acryloyl, styryl, acrylamide and methacrylamido.
- wherein n is equal to 1-10, n′ is equal to 2-4;
Cysteic acid 1 (0.5 mmols, 94 mg-L stereoisomer was used in this synthesis; however, D stereoisomer may also be used) was treated with an aqueous solution of tetrabutylammonium hydroxide (0.5 mmols, 4 mL of 0.125 M solution) at room temperature (scheme 1). After stirring for 30 min, the solution was lyophilized to give 2 and the residue was dissolved in dichloromethane (2 mL). Triethylamine (0.6 mmols, 61 mg) was added followed by the dropwise addition of HPTS-Cl (0.1 mmols, 52 mg) in dichloromethane (2 mL). The mixture stirred for 18 h at room temperature and was then concentrated in vacuo. The residue was dissolved in hot isopropyl alcohol and loaded onto a Biotage SP1 25M silica gel cartridge and eluted with NH4OH:isopropyl alcohol (1:3) to give HPTS-CysOH as a yellow powder (0.024 mmols, 39 mg, 24%). 1H NMR (D2O, 500 MHz) δ 0.85 (t, J=7.4 Hz, 36H), 1.20 (s, J=7.4 Hz, 24H) 1.44 (m, 24H), 2.94 (m, 24H), 3.24 (m, 6H), 4.31 (m, 3H), 8.19 (d, J=16.8 Hz, 2H), 8.36 (d, J=9.0 Hz, 1H), 8.50 (d, J=9.3 Hz, 1H), 8.64 (d, J=9.3 Hz, 1H), 8.71 (d, J=7.1 Hz, 1H), 8.90 (m, 4H), 9.19 (d, J=12.0 Hz, 2H).
To a solution of HPTS-CysOH (0.0183 mmols, 30 mg) in DMF (1 mL) was added N-ethyl-N′-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) (0.055 mmols 10.5 mg), 1-hydroxybenzotriazole (HOBT) (0.055 mmols, 7.4 mg), N,N,N′N′-tetramethyl-O-(1H-benzotriazol-1-yl)uronium hexafluorophosphate (HBTU) (0.055 mmols, 21 mg), and N,N′-diisopropylethylamine (DIEA) (0.183 mmols, 24 mg). After the solution was stirred at room temperature for 20 min, N-(3-aminopropyl)methacrylamide hydrochloride was added and the mixture was stirred for 48 h. The reaction mixture was precipitated with acetone:ether (5:1, 10 mL) to give an oily residue. The residue was triturated with acetone (10 mL) and sonicated for 30 min to give HPTS-CysMA as a crude mixture (35 mg of orange powder).
Step 1: Synthesis of TBCys:
In a 500-mL beaker equipped with a magnetic stirring bar, (L)-Cysteic acid (129.24 mmols, 24.1913 g) was dissolved in H2O (100 mL) and treated with tetrabutylammonium hydroxide (129.24 mmols, 129.24 mL, 128.59 g of a 1.0 M aqueous solution). The mixture was stirred at room temp for 30 min and then frozen using a low temperature (dry ice/2-propanol) bath. The solid was lyophilized over three days to give a glassy material that was re-dissolved in CH2Cl2 (300 mL). The solution was evaporated to dryness in a 500-mL flask to give TBCys as a white foam. Yield: 53.3756 g, 129 mmols, 100%.
Step 2: Synthesis of Phth Acid:
In a 500-mL flask equipped with a magnetic stirring bar, TBCys (129 mmols, 53.1936 g) was dissolved in CHCl3 (129 mL), and N,N′-diisopropylethyl amine (65 mmols, 8.385 g, 11.3 mL) was added followed by phthalic anhydride (129 mmols, 19.10748 g) and 4-angstrom molecular sieves (50 mL); the mixture was refluxed for 48 h. The mixture was filtered through a 600-mL glass fritted funnel and the filtrate was concentrated in vacuo and washed with diethyl ether (2×100 mL) and dried under reduced pressure to give Phth acid complexed with N,N′-diisopropylethyl amine. Yield: 70 g, 129 mmols, 100%. 1H NMR (CDCl3, 500 MHz) δ 0.95 (t, J=7.4 Hz, 12H), 1.30 (m, 8H), 1.38 (q, J=7.4 Hz, 8H), 1.61 (m, 8H), 2.96 (q, J=7.4 Hz, 1H), 3.23 (m, 8H), 3.55 (sept, J=6.7, 1H), 3.62 (m, 1H), 3.86 (dd, J1=5 Hz, J2=9.4 Hz, 1H), 5.31 (dd, J1=5.4 Hz, J2=1.2 Hz, 1H), 7.65 (q, J=3 Hz, 2H), 7.55 (q, J=3 Hz, 2H); 13C NMR (CDCl3, 125 MHz) δ 12.0, 13.8, 18.1, 19.8, 24.0, 41.7, 50.4, 51.0, 53.1, 58.7, 123.0, 132.8, 133.52, 167.9, 170.7; HPLC supelcosil LC-8-DB, 5 μm, 150 mm×4.6 mm, λ=254 nm, gradient elution (30 to 70% MeOH) with MeOH/TBAP, Rt=5.9 min.
Step 3: Synthesis of Phth MA:
In a 250-mL round bottom flask equipped with a magnetic stirring bar, Phth acid (24.9 mmols, 13.46 g) was dissolved in CH2Cl2 (85 mL) at 0° C. and EDC (27 mmols, 5.157 g), HOBT (27 mmols, 3.645 g), and triethylamine (54 mmols, 5.4 g, 7.5 mL) were added sequentially; the mixture was stirred under nitrogen for 20 min. N-(3-Aminopropyl)methacrylamide hydrochloride (27 mmols, 4.806 g) was added and the mixture was allowed to reach room temperature over 2 h and then was stirred for an additional 14 h at room temp. The solution was treated with sat. NaHCO3 (100 mL) and extracted with CH2Cl2 (3×20 mL). The CH2Cl2 layer was dried over MgSO4 and concentrated in vacuo to give an orange oil that was loaded onto a Biotage KP-sil 40M cartridge. The material was purified via gradient elution with 5 to 15% MeOH/CH2Cl2. The product was isolated as a white foam, yield 72%. 1H NMR (CDCl3, 500 MHz) δ 0.99 (t, J=7.4 Hz, 12H), 1.44 (sext, J=7.4 Hz, 8H), 1.66 (m, 10H), 1.89 (s, 3H), 3.28 (m, 1H), 3.38 (sext, 2H), 3.96 (dd, J1=9 Hz, J2=5.9 Hz, 1H), 5.22 (t, J=1.4 Hz, 1H), 5.44 (dd, J1=1.9 Hz, J2=9.0 Hz, 1H), 5.69 (s, 1H), 5.91 (t, J=6.0 Hz, 1H), 7.70 (m, 2H), 7.82 (m, 2H), 9.09 (t, J=5.8 Hz, 1H); 13C NMR (CDCl3, 125 MHz) δ 13.8, 18.7, 19.8, 24.1, 29.1, 36.0, 36.4, 50.5, 53.2, 58.9, 119.6, 123.4, 132.3, 134.0, 140.0, 167.9, 168.5, 169.3; HPLC supelcosil LC-8-DB, 5 μm, 150 mm×4.6 mm, λ=254 nm, gradient elution (30 to 70% MeOH) with MeOH/TBAP, Rt=6.6 min.
Step 4: Synthesis of AminoCysMA:
In a 100-mL round bottom flask equipped with a magnetic stirring bar, PhthMA (2.59 mmols, 1.7225 g) was dissolved in ethanol (20 mL) and hydrazine monohydrate (2.59 mmols, 0.130 g, 0.126 mL) was added and the mixture was heated at 80° C. for two hours. The solution was cooled to room temperature and CH2Cl2 (20 mL) was added. The precipitate that was formed was filtered using a fritted funnel and washed with additional CH2Cl2 (10 mL) and the filtrate was concentrated in vacuo. The residue was dissolved in CH2Cl2 (5 mL) and loaded onto a Biotage KP-NH 40M cartridge and eluted with 1% to 15% MeOH/CH2Cl2. The fractions were collected and concentrated in vacuo to give aminoCysMA as a colorless oil. Yield: 60%. 1H NMR (CD3OD, 500 MHz) δ 1.03 (t, J=7.4 Hz, 12H), 1.42 (sext, J=7.4 Hz, 8H), 1.66 (m, 8H), 1.95 (s, 3H), 2.87 (q, J1=9.4 Hz, J2=4.4 Hz, 1H), 3.23 (m, 10H), 3.81 (dd, J1=3.3 Hz, J2=6.0 Hz, 1H), 5.37 (s, 1H), 5.73 (s, 1H); HPLC supelcosil LC-8-DB, 5 μm, 150 mm×4.6 mm, λ=254 nm, gradient elution (30 to 70% MeOH) with MeOH/TBAP, Rt=3.5 min.
Step 5: Synthesis of HPTS-Cys-MA:
In a 50-mL round bottom flask, AminoCysMA (1.09 mmols, 0.5827 g) was dissolved in CH2Cl2 (10 mL) and HPTS-Cl (0.29 mmols, 0.163 g) was added. Triethylamine (1.1 mmols, 0.153 mL) was added and the mixture was stirred at room temperature for 16 h. The red solution was treated with 1 M NaOH (10 mL), stirred for 30 min., and the two layers were separated in a separatory funnel. The orange-aqueous layer was passed through a column of Dowex 50W resin (in the H+ form) to give a yellow/green solution with a pH=4 as determined by pH paper. The aqueous solution was then passed through a column of Dowex 50W (in the Na+ form) to obtain the crude sodium salt of HPTS-CysMA. The solution was adsorbed onto polystyrene-divinylbenzene resin (250 g) and washed with H2O (5×500 mL). The washings were kept and the adsorbed material was removed from the resin with MeOH (1 L). The MeOH/water extract was evaporated to dryness after multiple co-evaporations with fresh MeOH (4×500 mL) and the residue was re-dissolved in MeOH (0.5 mL). Acetone (15 mL) was added and the precipitate was collected by centrifugation and dried under a stream of argon to give HPTS-Cys-MA as an orange/yellow solid. Additional product was isolated from the washings using the same MeOH-extraction procedure. Yield: 40%. 1H-NMR (500 MHz, D2O, ppm): 1.18-1.09 (m, 6H), 1.76-1.53 (m, 9H), 2.73-2.23 (m, 12H); HPLC supelcosil LC-8-DB, 5 μm, 150 mm×4.6 mm, FLD detector, gradient elution (30 to 70% MeOH) with MeOH/TBAP, Rt=11.6 min; MALDI-TOF for C46H58N9Na3O22S6 [MH]+: 1350, [MH-Na+H]+:1328, [MH-2Na+2H]+: 1306, [MH-3Na+3H]+: 1284 (major).
As used herein, the term “quencher” refers to a compound that reduces the emission of a fluorescent dye, e.g., HPTS-Cys-MA, when in its presence.
In some embodiments, a quencher moiety provides glucose recognition. Such moieties preferably comprise an aromatic boronic acid. More specifically, the boronic acid is covalently bonded to a conjugated nitrogen-containing heterocyclic aromatic bis-onium structure (e.g., a viologen) in which the boronic acid reacts reversibly or irreversibly with glucose in aqueous, organic or combination media to form boronate esters. The extent of the reaction is related to glucose concentration in the medium.
Bis-onium salts are prepared from conjugated heterocyclic aromatic dinitrogen compounds. The conjugated heterocyclic aromatic dinitrogen are, e.g., dipyridyls, dipyridyl ethylenes, dipyridyl phenylenes, phenanthrolines, and diazafluorenes. It is understood that all isomers of said conjugated heterocyclic aromatic dinitrogen compounds in which both nitrogens can be substituted are useful in this invention. Boronic acid-substituted viologens and boronic acid-substituted polyviologens are described in detail in co-pending U.S. application Ser. No. 11/671,880; incorporated herein in its entirety by reference thereto.
In other embodiments, pyridinium boronic acid quenchers are used in combination with the dyes of the present invention. Pyridinium boronic acid quenchers are described in detail in U.S. Provisional Application No. 60/915,372; incorporated herein in its entirety by reference thereto.
In one preferred embodiment, 3,3′-oBBV may be used as a quencher moiety. The structure of 3,3′-oBBV is:
HPTS-Cys-MA was tested in solution using the fluorimeter to determine how it compares with HPTS-LysMA. Stern-Volmer and glucose response studies were carried out back to back under identical conditions to ensure direct comparison.
To a solution of HPTS-CysMA (1×10−5 M in pH 7.4 PBS) was added increasing amounts of 3,3′-oBBV (30 mM in MeOH) and the fluorescence emission measured after each addition.
HPTS-CysMA (1×10−5 M) and 3,3′-oBBV (3×10−3 M) were titrated with a stock solution of glucose (31250 mg/dL) in pH 7.4 PBS and the fluorescence emission measured after each addition of glucose The relative change upon addition of glucose is given in
HPTS-CysMA (1 mg), N,N′-dimethylacrylamide (400 mg), N,N′-methylenebisacrylamide (8 mg), HCl (10 μL of 1 M solution), and VA-044 (1 mg) were dissolved in water and diluted to 1 mL in a volumetric flask. The solution was freeze-pump-thawed (3×), injected into a mold containing a 0.005″ polyimide spacer and polymerized at 55° C. for 16 h. The resultant film was placed in pH 7.4 phosphate buffer and its fluorescence excitation and emission spectra obtained (
The film was tested in a flow cell configuration at various pHs (initially at pH 5.1; changed to pH 5.75, 6.26, 6.5, 6.9, 7.4, 8.02, and then back to pH 7.4) at two different excitation wavelengths (418 nm and 486 nm) and was monitored at one emission wavelength (532 nm) over time (
HPTS-CysMA (2 mg), 3,3′-oBBV (15 mg), N,N′-dimethylacrylamide (400 mg), N,N′-methylenebisacrylamide (8 mg), HCl (10 μL of 1 M solution), and VA-044 (1 mg) were dissolved in water and diluted to 1 mL in a volumetric flask. The solution was freeze-pump-thawed (3×), injected into a mold containing a 0.005″ polyimide spacer and polymerized at 55° C. for 16 h. The resultant film was placed in pH 7.4 phosphate buffer and was tested in a flow cell configuration with increasing amounts of glucose (0, 50, 100, 200, 400 mg/dL). The relative fluorescence change upon addition of glucose is given in
A comparison of the fluorescence spectra of the CysMA and LysMA dyes in solution is shown in
A comparison of the Stem-Volmer quenching study for CysMA and LysMA in solution is given in
HPTS-CysMA is quenched more effectively with 3,3′-oBBV than is HPTS-LysMA. HPTS-CysMA forms a stronger complex because of the sulfonic acids than does HPTS-LysMA, which has carboxylic acids; the tighter complex leads to a greater glucose response. For this reason, dyes substituted with sulfonate groups are preferred.
In one preferred embodiment, a device is disclosed for determining blood glucose concentration. The device comprises a sensor comprising an optical fiber sized for deployment intravascularly. The sensor further comprises a water-insoluble polymer matrix, wherein the polymer matrix is permeable to glucose; a fluorescent dye, as disclosed herein, associated with the polymer matrix; a quencher as disclosed herein, adapted to reversibly bind an amount of glucose related to the blood glucose concentration, wherein the quencher is also associated with the polymer matrix and operably coupled to the fluorescent dye, and wherein the quencher is configured to modulate the light emitted by the fluorescent dye related to the amount of bound glucose; at least one excitation light source; and an emission light detector.
A method is also disclosed for determining blood glucose concentration. The method comprises the steps of: providing the device described above; inserting the sensor into a blood vessel; irradiating the sensor at an excitation wavelength; detecting a fluorescence emission of the sensor at an emission wavelength; and determining the blood glucose concentration.
In some embodiments, for use in vitro not involving a moving stream, the sensing components are used as individual (discrete) components. The dye and quencher are mixed together in liquid solution, analyte is added, the change in fluorescence intensity is measured, and the components are discarded. Polymeric matrices that can be used to trap the sensing components to prevent leaching need not be present. Optionally, the sensing components are immobilized which allows their use to measure analytes in a moving stream.
For in vivo applications, the sensor is used in a moving stream of physiological fluid, preferably blood, which contains one or more polyhydroxyl organic compounds or is implanted in tissue such as muscle which contains said compounds. Therefore, it is preferred that none of the sensing moieties escape from the sensor assembly. Thus, for use in vivo, the sensing components are preferably part of an organic polymer sensing assembly. Soluble dyes and quenchers can be confined by a semi-permeable membrane that allows passage of the analyte but blocks passage of the sensing moieties. This can be realized by using soluble sensing moieties that are substantially larger than the analyte molecules (molecular weight of at least twice that of the analyte or greater than 1000 preferably greater than 5000); and employing a selectively semipermeable membrane such as a dialysis or an ultrafiltration membrane with a specific molecular weight cutoff between the two so that the sensing moieties are quantitatively retained.
Preferably the sensing moieties are immobilized in an insoluble polymer matrix, which is freely permeable to glucose. The polymer matrix is comprised of organic, inorganic or combinations of polymers thereof. The matrix may be composed of biocompatible materials. Alternatively, the matrix is coated with a second biocompatible polymer, and/or a semipermeable membrane, that is permeable to the analytes of interest.
The function of the polymer matrix is to hold together and immobilize the fluorescent dye and quencher moieties while at the same time allowing contact with the analyte, and binding of the analyte to the boronic acid. To achieve this effect, the matrix must be insoluble in the medium, and in close association with it by establishing a high surface area interface between matrix and analyte solution. For example, an ultra-thin film or microporous support matrix is used. Alternatively, the matrix is swellable in the analyte solution, e.g. a hydrogel matrix is used for aqueous systems. In some instances, the sensing polymers are bonded to a surface such as the surface of a light conduit, or impregnated in a microporous membrane. In all cases, the matrix must not interfere with transport of the analyte to the binding sites so that equilibrium can be established between the two phases. Techniques for preparing ultra-thin films, microporous polymers, microporous sol-gels, and hydrogels are established in the art. All useful matrices are defined as being analyte permeable.
While the present invention has been described in some detail for purposes of clarity and understanding, one skilled in the art will appreciate that various changes in form and detail can be made without departing from the true scope of the invention. All figures, tables, and appendices, as well as patents, applications, and publications, referred to above, are hereby incorporated by reference.