Analyte Monitoring Device and Methods of Use

Abstract

An analyte monitor includes a sensor, a sensor control unit, and a display unit. The sensor has, for example, a substrate, a recessed channel formed in the substrate, and conductive material disposed in the recessed channel to form a working electrode. The sensor control unit typically has a housing adapted for placement on skin and is adapted to receive a portion of an electrochemical sensor. The sensor control unit also includes two or more conductive contacts disposed on the housing and configured for coupling to two or more contact pads on the sensor. A transmitter is disposed in the housing and coupled to the plurality of conductive contacts for transmitting data obtained using the sensor. The display unit has a receiver for receiving data transmitted by the transmitter of the sensor control unit and a display coupled to the receiver for displaying an indication of a level of an analyte. The analyte monitor may also be part of a drug delivery system to alter the level of the analyte based on the data obtained using the sensor.

1 - 120 . (canceled) 
     
     
         121 . An analyte sensor unit comprising:
 a housing adapted for placement on the surface of skin having a bottom surface for contacting with the skin and wherein the housing comprises:
 an electrochemical sensor within the housing so that the electrochemical sensor is inserted to a depth of about 2 to about 7 mm beneath the surface of the skin, wherein the electrochemical sensor comprises a working electrode comprising an analyte-responsive enzyme and a mediator and wherein at least one of the analyte-responsive enzyme and the mediator is chemically bonded to a polymer disposed on the working electrode; 
 an RF communication unit for communicating data obtained by the electrochemical sensor; and 
 factory determined calibration information for the electrochemical sensor accessible on a readable or readable/writable memory for calibrating the electrochemical sensor, wherein the electrochemical sensor does not require user-implemented calibration following insertion of a portion of the sensor beneath the surface of the skin; and 
   an adhesive disposed on the bottom surface of the housing to attach the housing to the surface of the skin.   
     
     
         122 . The analyte sensor unit of  claim 121 , wherein the electrochemical sensor is inserted beneath the surface of the skin at a position located substantially beneath the housing when the housing is placed on the skin. 
     
     
         123 . The analyte sensor unit of  claim 121 , wherein the electrochemical sensor has a length of about 0.3 to about 5 cm and comprises a proximal end that is in contact with electrical contacts within the housing and a distal end that extends through an opening at the bottom of the housing. 
     
     
         124 . The analyte sensor unit of  claim 123 , wherein at least a portion of the distal end of the electrochemical sensor is bent so that a portion of the sensor is in a plane substantially perpendicular to the electrical contacts in the housing. 
     
     
         125 . The analyte sensor unit of  claim 123 , wherein the distal end of the electrochemical sensor has a length of up to about 6 mm. 
     
     
         126 . The analyte sensor unit of  claim 123 , wherein the electrochemical sensor has a length of up to about 2 cm. 
     
     
         127 . The analyte sensor unit of  claim 121 , wherein the housing comprises a data storage unit to store analyte data obtained by the electrochemical sensor. 
     
     
         128 . The analyte sensor unit of  claim 121 , wherein the analyte sensor unit automatically detects use following insertion by transitioning from a sleep mode to an active mode. 
     
     
         129 . The analyte sensor unit of  claim 128 , wherein automatically detecting use comprises detecting a change in resistance in the electrochemical sensor. 
     
     
         130 . The analyte sensor unit of  claim 129 , wherein automatically detecting use further comprises activating the analyte sensor unit. 
     
     
         131 . The analyte sensor unit of  claim 121 , wherein the RF communication unit receives data from a second RF communication unit of a display unit. 
     
     
         132 . The analyte sensor unit of  claim 131 , wherein data received by the RF communication unit comprises an activation signal. 
     
     
         133 . The analyte sensor unit of  claim 121 , wherein the electrochemical sensor is comprises a proximal end is in contact with electrical contacts within the housing and a distal end that extends through an opening at the bottom of the housing. 
     
     
         134 . The analyte sensor unit of  claim 133 , wherein the electrical contacts are disposed on an interior surface of the housing. 
     
     
         135 . The analyte sensor unit of  claim 121 , further comprising a processor to determine the rate of change of the glucose. 
     
     
         136 . The analyte sensor unit of  claim 121 , further comprising a processing circuit disposed in the housing for determining a level of an analyte from a signal generated by the electrochemical sensor. 
     
     
         137 . The analyte sensor unit of  claim 136 , wherein the processing circuit is adjusts the data for temperature using a signal from a temperature probe of the sensor. 
     
     
         138 . The analyte sensor unit of  claim 121 , wherein at least one of the analyte-responsive enzyme and the mediator is covalently bonded to the polymer. 
     
     
         139 . The analyte sensor unit of  claim 138 , wherein at least one of the analyte-responsive enzyme and the mediator forms one or more of carbon-carbon, carbon-nitrogen, or metal-carbon covalent bonds with the polymer. 
     
     
         140 . The analyte sensor unit of  claim 138 , wherein at least one of the analyte-responsive enzyme and the mediator is covalently bonded to the polymer through a linker moiety. 
     
     
         141 . The analyte sensor unit of  claim 138 , wherein the mediator is covalently bonded to the polymer through one or more ligands of the mediator. 
     
     
         142 . The analyte sensor unit of  claim 141 , wherein the one or more ligands comprises a substituted or unsubstituted heterocyclic nitrogen-containing moiety. 
     
     
         143 . The analyte sensor unit of  claim 138 , wherein one or more ligands of the mediator are substituents of the polymer backbone. 
     
     
         144 . The analyte sensor unit of  claim 138 , wherein the analyte-responsive enzyme is covalently bonded to the polymer through one or more side chains of the enzyme. 
     
     
         145 . The analyte sensor unit of  claim 144 , wherein the one or more side chains of the analyte-responsive enzyme is selected from the group consisting of substituted or unsubstituted amines, alcohols, thiols, phenols, imidazoles, indols, and carboxylic acids. 
     
     
         146 . The analyte sensor unit of  claim 138 , wherein one or more side chains of the analyte-responsive enzyme are substituents of the polymer backbone. 
     
     
         147 . The analyte sensor unit of  claim 121 , wherein the polymer is crosslinked. 
     
     
         148 . The analyte sensor unit of  claim 138 , wherein at least one of the analyte-responsive enzyme and the mediator is crosslinked with the polymer. 
     
     
         149 . The analyte sensor unit of  claim 148 , wherein at least one of the analyte-responsive enzyme and the mediator is crosslinked with the polymer through one or more cros slinking agents. 
     
     
         150 . The analyte sensor unit of  claim 149 , wherein the one or more crosslinking agents is selected from the group consisting of substituted or unsubstituted epoxides, aldehydes, imidoesters, N-hydroxysuccinimide esters, carbodiimides, cyanuric chloride, tetrachlorobenzoquinone, benzoquinone and tetracyanoquinodimethane. 
     
     
         151 . The analyte sensor unit of  claim 148 , wherein one or more ligands of the mediator are crosslinkers of the polymer. 
     
     
         152 . The analyte sensor unit of  claim 148 , wherein one or more side chains of the analyte-responsive enzyme are crosslinkers of the polymer. 
     
     
         153 . The analyte sensor unit of  claim 121 , wherein the polymer forms a coordination complex with the mediator. 
     
     
         154 . The analyte sensor unit of  claim 153 , wherein one or more nitrogen-containing moieties of the polymer forms a coordination complex with a metal of the mediator. 
     
     
         155 . The analyte sensor unit of  claim 121 , wherein the mediator is ionically bonded to the polymer. 
     
     
         156 . The analyte sensor unit of  claim 155 , wherein the polymer comprises at least one positively charged moiety and the mediator comprises at least one negatively charged moiety. 
     
     
         157 . The analyte sensor unit of  claim 155 , wherein the polymer comprises at least one negatively charged moiety and the mediator comprises at least one positively charged moiety. 
     
     
         158 . The analyte sensor unit of  claim 121 , wherein the polymer is chemically bonded to the surface of the working electrode. 
     
     
         159 . The analyte sensor unit of  claim 121 , wherein the sensing layer membrane is formed in situ on the working electrode. 
     
     
         160 . The analyte sensor unit of  claim 159 , wherein the sensing layer membrane is formed in situ on the working electrode by crosslinking the polymer on the working electrode. 
     
     
         161 . The analyte sensor unit of  claim 159 , wherein the working electrode further comprises a mass transport limiting membrane disposed over the sensing layer membrane. 
     
     
         162 . The analyte sensor unit of  claim 121 , wherein the analyte-responsive enzyme is a glucose-responsive enzyme. 
     
     
         163 . The analyte sensor unit of  claim 121 , wherein the analyte-responsive enzyme is glucose dehydrogenase (GDH) or glucose oxidase (GOx). 
     
     
         164 . The analyte sensor unit of  claim 121 , wherein the analyte-responsive enzyme further comprises an enzyme cofactor. 
     
     
         165 . The analyte sensor unit of  claim 164 , wherein the enzyme cofactor is flavin adenine dinucleotide. 
     
     
         166 . The analyte sensor unit of  claim 121 , wherein the mediator comprises ruthenium or osmium. 
     
     
         167 . An analyte monitoring system for determining the concentration of an analyte comprising:
 an analyte sensor unit comprising:
 a housing adapted for placement on the surface of skin having a bottom surface for contacting with the skin and wherein the housing comprises:
 an electrochemical sensor within the housing so that the electrochemical sensor is inserted to a depth of about 2 to about 7 mm beneath the surface of the skin, wherein the electrochemical sensor comprises a working electrode comprising an analyte-responsive enzyme and a mediator and wherein at least one of the analyte-responsive enzyme and the mediator is chemically bonded to a polymer disposed on the working electrode; 
 an RF communication unit for communicating data obtained by the electrochemical sensor; and 
 factory determined calibration information for the electrochemical sensor accessible on a readable or readable/writable memory for calibrating the electrochemical sensor, wherein the electrochemical sensor does not require user-implemented calibration following insertion of a portion of the sensor beneath the surface of the skin; and 
 
 an adhesive disposed on the bottom surface of the housing to attach the housing to the surface of the skin; and 
   a display unit comprising a housing, wherein the housing comprises:
 a second RF communication unit for communicating with the first wireless communication unit; and 
 a display to display the concentration of an analyte. 
   
     
     
         168 . The analyte monitoring system of  claim 167 , wherein the electrochemical sensor is inserted beneath the surface of the skin at a position located substantially beneath the housing when the housing is placed on the skin. 
     
     
         169 . The analyte monitoring system of  claim 167 , wherein the electrochemical sensor has a length of about 0.3 to about 5 cm and that a proximal end of the electrochemical sensor is in contact with electrical contacts within the housing and a distal of the electrochemical sensor extends through an opening at the bottom of the housing. 
     
     
         170 . The analyte monitoring system of  claim 169 , wherein at least a portion of the distal end of the electrochemical sensor is bent so that a portion of the sensor is in a plane substantially perpendicular to the electrical contacts in the housing. 
     
     
         171 . The analyte monitoring system of  claim 169 , wherein the distal end of the electrochemical sensor has a length of up to about 6 mm. 
     
     
         172 . The analyte monitoring system of  claim 169 , wherein the electrochemical sensor has a length of up to about 2 cm. 
     
     
         173 . The analyte monitoring system of  claim 167 , wherein the analyte sensor unit automatically detects use following insertion by transitioning from a sleep mode to an active mode. 
     
     
         174 . The analyte monitoring system of  claim 173 , wherein automatically detecting use comprises detecting a change in resistance in the electrochemical sensor. 
     
     
         175 . The analyte monitoring system of  claim 174 , wherein automatically detecting use further comprises activating the analyte sensor unit. 
     
     
         176 . The analyte monitoring system of  claim 167 , wherein the first RF communication unit receives data from a second RF communication unit of a display unit. 
     
     
         177 . The analyte monitoring system of  claim 176 , wherein data received by the RF communication unit comprises an activation signal. 
     
     
         178 . The analyte monitoring system of  claim 169 , wherein the electrical contacts are disposed on an interior surface of the housing. 
     
     
         179 . The analyte monitoring system of  claim 167 , further comprising a processing circuit disposed in the housing for determining a level of an analyte from a signal generated by the electrochemical sensor. 
     
     
         180 . The analyte monitoring system of  claim 167 , wherein at least one of the analyte-responsive enzyme and the mediator is covalently bonded to the polymer. 
     
     
         181 . The analyte monitoring system of  claim 180 , wherein at least one of the analyte-responsive enzyme and the mediator is covalently bonded to the polymer through a linker moiety. 
     
     
         182 . The analyte monitoring system of  claim 180 , wherein the mediator is covalently bonded to the polymer through one or more ligands of the mediator. 
     
     
         183 . The analyte monitoring system of  claim 167 , wherein the polymer is crosslinked. 
     
     
         184 . The analyte monitoring system of  claim 183 , wherein at least one of the analyte-responsive enzyme and the mediator is crosslinked with the polymer. 
     
     
         185 . An analyte monitoring system for determining the concentration of an analyte comprising:
 an analyte sensor unit comprising:
 a housing adapted for placement on the surface of skin having a bottom surface for contacting with the skin and wherein the housing comprises:
 an electrochemical sensor within the housing so that the electrochemical sensor is inserted to a depth of about 2 to about 7 mm beneath the surface of the skin, wherein the electrochemical sensor comprises a working electrode comprising an analyte-responsive enzyme and a mediator and wherein at least one of the analyte-responsive enzyme and the mediator is chemically bonded to a polymer disposed on the working electrode; 
 an RF communication unit for communicating data obtained by the electrochemical sensor; and 
 factory determined calibration information for the electrochemical sensor accessible on a readable or readable/writable memory for calibrating the electrochemical sensor, wherein the electrochemical sensor does not require user-implemented calibration following insertion of a portion of the sensor beneath the surface of the skin; and 
 
 an adhesive disposed on the bottom surface of the housing to attach the housing to the surface of the skin; and 
   a display unit comprising a housing, wherein the housing comprises:
 a second RF communication unit configured to communicate with the first wireless communication unit; 
 a display for displaying the concentration of an analyte; and 
 a test port to receive an in-vitro analyte sensor. 
   
     
     
         186 . The analyte monitoring system of  claim 185 , wherein the electrochemical sensor is inserted beneath the surface of the skin at a position located substantially beneath the housing when the housing is placed on the skin. 
     
     
         187 . The analyte monitoring system of  claim 185 , wherein the electrochemical sensor has a length of about 0.3 to about 5 cm and that a proximal end of the electrochemical sensor is in contact with electrical contacts within the housing and a distal end of the electrochemical sensor extends through an opening at the bottom of the housing. 
     
     
         188 . The analyte monitoring system of  claim 187 , wherein at least a portion of the distal end of the electrochemical sensor is bent so that a portion of the sensor is in a plane substantially perpendicular to the electrical contacts in the housing. 
     
     
         189 . The analyte monitoring system of  claim 187 , wherein the distal end of the electrochemical sensor has a length of up to about 6 mm. 
     
     
         190 . The analyte monitoring system of  claim 187 , wherein the electrochemical sensor has a length of up to about 2 cm. 
     
     
         191 . The analyte monitoring system of  claim 185 , wherein the analyte sensor unit is automatically detects use following insertion by transitioning from a sleep mode to an active mode. 
     
     
         192 . The analyte monitoring system of  claim 191 , wherein automatically detecting use comprises detecting a change in resistance in the electrochemical sensor. 
     
     
         193 . The analyte monitoring system of  claim 192 , wherein automatically detecting use further comprises activating the analyte sensor unit. 
     
     
         194 . The analyte monitoring system of  claim 185 , wherein the first RF communication unit to receives data from a second RF communication unit of a display unit. 
     
     
         195 . The analyte monitoring system of  claim 194 , wherein data received by the first RF communication unit comprises an activation signal. 
     
     
         196 . The analyte monitoring system of  claim 187 , wherein the electrical contacts are disposed on an interior surface of the housing. 
     
     
         197 . The analyte monitoring system of  claim 185 , further comprising a processing circuit disposed in the housing for determining a level of an analyte from a signal generated by the electrochemical sensor. 
     
     
         198 . The analyte monitoring system of  claim 185 , wherein at least one of the analyte-responsive enzyme and the mediator is covalently bonded to the polymer. 
     
     
         199 . The analyte monitoring system of  claim 185 , wherein at least one of the analyte-responsive enzyme and the mediator is covalently bonded to the polymer through a linker moiety. 
     
     
         200 . The analyte monitoring system of  claim 185 , wherein the mediator is covalently bonded to the polymer through one or more ligands of the mediator. 
     
     
         201 . The analyte monitoring system of  claim 185 , wherein the polymer is crosslinked. 
     
     
         202 . The analyte monitoring system of  claim 201 , wherein at least one of the analyte-responsive enzyme and the mediator is crosslinked with the polymer. 
     
     
         203 . A method for attaching an analyte sensor unit to the skin of a patient, the method comprising:
 contacting an insertion device coupled with an analyte sensor unit to the skin of a patient; the analyte sensor unit comprising:
 a housing adapted for placement on the surface of skin having a bottom surface for contacting with the skin and wherein the housing comprises:
 an electrochemical sensor within the housing so that the electrochemical sensor is inserted to a depth of about 2 to about 7 mm beneath the surface of the skin, wherein the electrochemical sensor comprises a working electrode comprising an analyte-responsive enzyme and a mediator and wherein at least one of the analyte-responsive enzyme and the mediator is chemically bonded to a polymer disposed on the working electrode; 
 an RF communication unit for communicating data obtained by the electrochemical sensor; and 
 factory determined calibration information for the electrochemical sensor accessible on a readable or readable/writable memory for calibrating the electrochemical sensor, wherein the electrochemical sensor does not require user-implemented calibration following insertion of a portion of the sensor beneath the surface of the skin; and 
 
 an adhesive disposed on the bottom surface of the housing to attach the housing to the surface of the skin; 
   applying manual pressure to the insertion device coupled with the analyte sensor unit to attach the analyte sensor unit to the skin using the adhesive;   inserting at least a portion of the electrochemical sensor to a depth of about 2.0 to about 7 mm beneath the surface of the skin; and   decoupling the insertion device from the sensor control unit.   
     
     
         204 . The method of  claim 203 , wherein the inserter is U-shaped or V-shaped. 
     
     
         205 . The method of  claim 203 , wherein the electrochemical sensor is inserted beneath the surface of the skin at a position located substantially beneath the housing when the housing is placed on the skin. 
     
     
         206 . The method of  claim 203 , wherein the electrochemical sensor has a length of about 0.3 to about 5 cm so that a proximal end is in contact with electrical contacts within the housing and at least a portion of a distal end of the electrochemical sensor extends through an opening at the bottom of the housing. 
     
     
         207 . The method of  claim 206 , wherein at least a portion of the distal end of the electrochemical sensor is bent so that a portion of the sensor is in a plane substantially perpendicular to the electrical contacts in the housing. 
     
     
         208 . The method of  claim 206 , wherein the distal end of the electrochemical sensor has a length of up to about 6 mm. 
     
     
         209 . The method of  claim 206 , wherein the electrochemical sensor has a length of up to about 2 cm. 
     
     
         210 . The method of  claim 203 , wherein the analyte sensor unit automatically detects use following insertion by transitioning from a sleep mode to an active mode. 
     
     
         211 . The method of  claim 210 , wherein automatically detecting use comprises detecting a change in resistance in the electrochemical sensor. 
     
     
         212 . The method of  claim 211 , wherein automatically detecting use further comprises activating the analyte sensor unit. 
     
     
         213 . The method of  claim 203 , wherein the RF communication unit receives data from a second RF communication unit of a display unit. 
     
     
         214 . The method of  claim 213 , wherein data received by the RF communication unit comprises an activation signal. 
     
     
         215 . The method of  claim 206 , wherein the electrochemical sensor comprises a proximal end in contact with electrical contacts within the housing and a distal end extending through an opening at the bottom of the housing. 
     
     
         216 . The method of  claim 215 , wherein the electrical contacts are disposed on an interior surface of the housing. 
     
     
         217 . The method of  claim 203 , further comprising a processing circuit disposed in the housing for determining a level of an analyte from a signal generated by the electrochemical sensor. 
     
     
         218 . The method of  claim 203 , wherein at least one of the analyte-responsive enzyme and the mediator is covalently bonded to the polymer. 
     
     
         219 . The method of  claim 218 , wherein at least one of the analyte-responsive enzyme and the mediator is covalently bonded to the polymer through a linker moiety. 
     
     
         220 . The method of  claim 218 , wherein the mediator is covalently bonded to the polymer through one or more ligands of the mediator. 
     
     
         221 . The method of  claim 203 , wherein the polymer is crosslinked. 
     
     
         222 . A method for monitoring the concentration of an analyte, the method comprising:
 contacting an insertion device coupled with an analyte sensor unit to the skin of a patient; the analyte sensor unit comprising:
 a housing adapted for placement on the surface of skin having a bottom surface for contacting with the skin and wherein the housing comprises:
 an electrochemical sensor within the housing so that the electrochemical sensor is inserted to a depth of about 2 to about 7 mm beneath the surface of the skin, wherein the electrochemical sensor comprises a working electrode comprising an analyte-responsive enzyme and a mediator and wherein at least one of the analyte-responsive enzyme and the mediator is chemically bonded to a polymer disposed on the working electrode; 
 an RF communication unit for communicating data obtained by the electrochemical sensor; and 
 factory determined calibration information for the electrochemical sensor accessible on a readable or readable/writable memory for calibrating the electrochemical sensor, wherein the electrochemical sensor does not require user-implemented calibration following insertion of a portion of the sensor beneath the surface of the skin; and 
 
 an adhesive disposed on the bottom surface of the housing to attach the housing to the surface of the skin; 
   applying manual pressure to the insertion device coupled with the analyte sensor unit to attach the analyte sensor unit to the skin using the adhesive;   inserting at least a portion of the electrochemical sensor to a depth of about 2 to about 7 mm beneath the surface of the skin;   decoupling the insertion device from the sensor control unit;   collecting data from the electrochemical sensor corresponding to the analyte;   communicating the data to a display unit comprising a second RF communication unit and a display unit; and   displaying a concentration of the analyte on the display unit.   
     
     
         223 . The method of  claim 222 , wherein the inserter is U-shaped or V-shaped. 
     
     
         224 . The method of  claim 222 , wherein the electrochemical sensor is inserted beneath the surface of the skin at a position located substantially beneath the housing when the housing is placed on the skin. 
     
     
         225 . The method of  claim 222 , wherein the electrochemical sensor has a length of about 0.3 to about 5 cm so that a proximal end is in contact with electrical contacts within the housing and at least a portion of a distal end of the electrochemical sensor extends through an opening at the bottom of the housing. 
     
     
         226 . The method of  claim 225 , wherein at least a portion of the distal end of the electrochemical sensor is bent so that a portion of the sensor is in a plane substantially perpendicular to the electrical contacts in the housing. 
     
     
         227 . The method of  claim 225 , wherein the distal end of the electrochemical sensor has a length of up to about 6 mm. 
     
     
         228 . The method of  claim 225 , wherein the electrochemical sensor has a length of up to about 2 cm. 
     
     
         229 . The method of  claim 222 , wherein the analyte sensor unit is automatically detects use following insertion by transitioning from a sleep mode to an active mode. 
     
     
         230 . The method of  claim 229 , wherein automatically detecting use comprises detecting a change in resistance in the electrochemical sensor. 
     
     
         231 . The method of  claim 230 , wherein automatically detecting use further comprises activating the analyte sensor unit. 
     
     
         232 . The method of  claim 222 , wherein the RF communication unit receives data from a second RF communication unit of a display unit. 
     
     
         233 . The method of  claim 232 , wherein data received by the RF communication unit comprises an activation signal. 
     
     
         234 . The method of  claim 225 , wherein the electrochemical sensor comprises a proximal end in contact with electrical contacts within the housing and a distal end extending through an opening at the bottom of the housing. 
     
     
         235 . The method of  claim 234 , wherein the electrical contacts are disposed on an interior surface of the housing. 
     
     
         236 . The method of  claim 222 , further comprising a processing circuit disposed in the housing for determining a level of an analyte from a signal generated by the electrochemical sensor. 
     
     
         237 . The method of  claim 222 , wherein at least one of the analyte-responsive enzyme and the mediator is covalently bonded to the polymer. 
     
     
         238 . The method of  claim 237 , wherein at least one of the analyte-responsive enzyme and the mediator is covalently bonded to the polymer through a linker moiety. 
     
     
         239 . The method of  claim 237 , wherein the mediator is covalently bonded to the polymer through one or more ligands of the mediator. 
     
     
         240 . The method of  claim 222 , wherein the polymer is crosslinked.