Tissue implantable sensors for measurement of blood solutes

Abstract

A tissue-implantable sensor for measurement of solutes in fluids and gases, such as oxygen and glucose, is provided. The sensor includes a multiplicity of detectors, constructed and arranged to improve the probability that one or more detectors will have access to a vascular source at points in time sufficient to permit accurate measurements to be taken. Means and methods for calculating solute levels using the sensor device of the invention are also provided.

1 . A device for estimating the concentration of an analyte in a biological environment, said device comprising: 
 (a) a body;    (b) at least two primary detectors disposed on the body, wherein each primary detector is adapted to produce a signal responsive to the concentration of the analyte in the immediate biological microenvironment; and,    (c) signal processing means in communication with each individual primary detector for receiving a signal therefrom and estimating the concentration of the analyte in the biological environment from the signals said signal processing means employing one or more predetermined algorithms, said signal processing means comprising: 
 (i) means for adjusting the signals from each primary detector by applying signal adjustment coefficients thereto, wherein the coefficients compensate for detector failure, detector drift or variations between the biological microenvironments occupied by each detector;  
 (ii) means for estimating the analyte concentration in the biological microenvironment of individual primary detectors; and  
 (iii) means for estimating the concentration of the analyte by mathematical calculation of a primary composite signal indicative of said analyte concentration.  
   
     
     
         2 . The device according to  claim 1 , further comprising at least one secondary detector disposed on the body, wherein each secondary detector is adapted to produce a signal responsive to one or more confounding phenomena in the biological microenvironment occupied by at least one primary detector.  
     
     
         3 . The device according to  claim 2 , further comprising signal processing means in communication with each individual secondary detector for receiving a signal responsive to the presence of a confounding phenomenon in the biological microenvironment occupied by at least one primary detector.  
     
     
         4 . The device according to  claim 3 , further comprising signal processing means in communication with each individual secondary detector for receiving a signal responsive to the magnitude of a confounding phenomenon in the biological microenvironment occupied by the secondary detector.  
     
     
         5 . The device according to  claim 1 , further comprising means for calibrating the signal adjustment coefficients.  
     
     
         6 . The device according to  claim 1 , wherein the biological environment comprises human tissue.  
     
     
         7 . The device according to  claim 1 , wherein the analyte is glucose.  
     
     
         8 . The device according to  claim 1 , wherein the primary detector incorporates glucose oxidase.  
     
     
         9 . The device according to  claim 3 , wherein at least one confounding phenomenon comprises a concentration of a substance other than the analyte.  
     
     
         10 . The device according to  claim 9 , wherein the at least one confounding phenomenon comprises the concentration of oxygen.  
     
     
         11 . The device according to  claim 9 , wherein the at least one confounding phenomenon comprises the temperature.  
     
     
         12 . The device according to  claim 9 , wherein the at least one confounding phenomenon comprises the heart rate.  
     
     
         13 . The device according to  claim 9 , wherein the at least one confounding phenomenon comprises the respiratory rate.  
     
     
         14 . The device according to  claim 9 , wherein the at least one confounding phenomenon comprises the physical activity level.  
     
     
         15 . The device according to  claim 9 , wherein the at least one confounding phenomenon comprises muscular activity.  
     
     
         16 . The device according to  claim 1 , wherein the detector areas of adjacent detectors do not overlap.  
     
     
         17 . The device according to  claim 1 , wherein each effective detector radius is between 20 μm and 200 μm.  
     
     
         18 . The device according to  claim 1 , wherein the means for estimating the concentration of an analyte comprises utilizing detector signals, signal adjustment coefficients, and at least one predetermined formula to calculate a value of analyte concentration representative of the biological environment.  
     
     
         19 . A method for estimating the concentration of an analyte in a biological environment, the method comprising reading a primary composite signal indicative of the analyte concentration from a display in communication with signal processing means in a device according to  claim 1 .  
     
     
         20 . The method according to  claim 19 , wherein the device is implanted in a human tissue.  
     
     
         21 . A method for calibrating the device of  claim 1 , the method comprising adjusting one or more detector signals obtained from the device to zero in the absence of external stimuli.  
     
     
         22 . A method for calibrating the device of  claim 1 , the method comprising adjusting one or more detector signals obtained from the device to reflect the signal expected in response to a known stimulus.  
     
     
         23 . A device for estimating the concentration of an analyte in a biological environment, said device comprising: 
 (a) a body;    (b) at least two primary detectors disposed on the body, wherein each primary detector is adapted to produce a signal responsive to the concentration of the analyte in the immediate biological microenvironment; and,    (c) signal processing means in communication with each individual primary detector for receiving a signal therefrom and estimating the concentration of the analyte in the biological environment from the signals said signal processing means employing one or more predetermined algorithms, said signal processing means comprising: 
 (i) means for estimating the analyte concentration in the biological microenvironment of individual primary detectors;  
 (ii) means for adjusting the analyte concentration estimates by applying signal adjustment coefficients thereto, wherein the coefficients compensate for detector failure, detector drift or variations between the biological microenvironments occupied by each detector; and,  
 (iii) means for estimating the concentration of the analyte by mathematical calculation of a primary composite signal indicative of said analyte concentration.  
   
     
     
         24 . The device according to  claim 23 , further comprising at least one secondary detector disposed on the body, wherein each secondary detector is adapted to produce a signal responsive to one or more confounding phenomena in the biological microenvironment occupied by at least one primary detector.  
     
     
         25 . The device according to  claim 24 , further comprising signal processing means in communication with each individual secondary detector for receiving a signal responsive to the presence of a confounding phenomenon in the biological microenvironment occupied by at least one primary detector.  
     
     
         26 . The device according to  claim 25 , further comprising signal processing means in communication with each individual secondary detector for receiving a signal responsive to the magnitude of a confounding phenomenon in the biological microenvironment occupied by the secondary detector.  
     
     
         27 . The device according to  claim 23 , further comprising means for calibrating the signal adjustment coefficients.  
     
     
         28 . The device according to  claim 23 , wherein the biological environment comprises human tissue.  
     
     
         29 . The device according to  claim 23 , wherein the analyte is glucose.  
     
     
         30 . The device according to  claim 23 , wherein the primary detector incorporates glucose oxidase.  
     
     
         31 . The device according to  claim 24 , wherein at least one confounding phenomenon comprises a concentration of a substance other than the analyte.  
     
     
         32 . The device according to  claim 31 , wherein the at least one confounding phenomenon comprises the concentration of oxygen.  
     
     
         33 . The device according to  claim 31 , wherein the at least one confounding phenomenon comprises the temperature.  
     
     
         34 . The device according to  claim 31 , wherein the at least one confounding phenomenon comprises the heart rate.  
     
     
         35 . The device according to  claim 31 , wherein the at least one confounding phenomenon comprises the respiratory rate.  
     
     
         36 . The device according to  claim 31 , wherein the at least one confounding phenomenon comprises the physical activity level.  
     
     
         37 . The device according to  claim 31 , wherein the at least one confounding phenomenon comprises muscular activity.  
     
     
         38 . The device according to  claim 23 , wherein the detector areas of adjacent detectors do not overlap.  
     
     
         39 . The device according to  claim 23 , wherein each effective detector radius is between 20 μm and 200 μm.  
     
     
         40 . The device according to  claim 23 , wherein the means for estimating the concentration of an analyte comprises utilizing detector signals, signal adjustment coefficients, and at least one predetermined formula to calculate a value of analyte concentration representative of the biological environment.  
     
     
         41 . A method for estimating the concentration of an analyte in a biological environment, the method comprising reading a primary composite signal indicative of the analyte concentration from a display in communication with signal processing means in a device according to  claim 1 .  
     
     
         42 . The method according to  claim 41 , wherein the device is implanted in a human tissue.  
     
     
         43 . A method for calibrating the device of  claim 23 , the method comprising adjusting one or more detector signals obtained from the device to zero in the absence of external stimuli.  
     
     
         44 . A method for calibrating the device of  claim 23 , the method comprising adjusting one or more detector signals obtained from the device to reflect the signal expected in response to a known stimulus.  
     
     
         45 . A device for estimating the concentration of an analyte in a biological environment, said device comprising: 
 (a) a body;    (b) at least one primary detector disposed on the body, wherein each primary detector is adapted to produce a signal responsive to the concentration of the analyte in the immediate biological microenvironment;    (c) a plurality of secondary detectors disposed on the body, wherein each secondary detector is adapted to produce a signal responsive to one or more confounding phenomena in the biological microenvironment of at least one primary detector; and,    (d) signal processing means in communication with each individual detector for receiving a signal therefrom, said signal processing means comprising: 
 (i) means for adjusting the signals from each secondary detector by applying signal adjustment coefficients thereto, wherein the coefficients compensate for detector failure, detector drift, variations between the biological microenvironments occupied by each detector, and confounding phenomena; and,  
 (ii) means for estimating the analyte concentration in the biological microenvironment of each individual primary detector; and  
 (iii) means for adjusting the estimated analyte concentration associated with each primary detector by applying signal adjustment coefficients thereto, wherein the coefficients compensate for detector failure, detector drift, variations between the biological microenvironments occupied by each detector, and confounding phenomena; and  
 (iv) means for estimating the concentration of the analyte by mathematical calculation of a primary composite signal indicative of said analyte concentration.  
   
     
     
         46 . The device according to  claim 45 , further comprising means for calibrating the signal adjustment coefficients.  
     
     
         47 . The device according to  claim 45 , wherein the biological environment comprises human tissue.  
     
     
         48 . The device according to  claim 45 , wherein the analyte is glucose.  
     
     
         49 . The device according to  claim 45 , wherein the primary detector incorporates glucose oxidase.  
     
     
         50 . The device according to  claim 45 , wherein at least one confounding phenomenon comprises a concentration of a substance other than the analyte.  
     
     
         51 . The device according to  claim 50 , wherein the at least one confounding phenomenon comprises the concentration of oxygen.  
     
     
         52 . The device according to  claim 45 , wherein the at least one confounding phenomenon comprises the temperature.  
     
     
         53 . The device according to  claim 45 , wherein the at least one confounding phenomenon comprises the heart rate.  
     
     
         54 . The device according to  claim 45 , wherein the at least one confounding phenomenon comprises the respiratory rate.  
     
     
         55 . The device according to  claim 45 , wherein the at least one confounding phenomenon comprises the physical activity level.  
     
     
         56 . The device according to  claim 45 , wherein the at least one confounding phenomenon comprises muscular activity.  
     
     
         57 . The device according to  claim 45 , wherein the detector areas of adjacent detectors do not overlap.  
     
     
         58 . The device according to  claim 45 , wherein each effective detector radius is between 20 μm and 200 μm.  
     
     
         59 . The device according to  claim 45 , wherein the means for estimating the concentration of an analyte comprises utilizing detector signals, signal adjustment coefficients, and at least one predetermined formula to calculate a value of analyte concentration representative of the biological environment.  
     
     
         60 . The device according to  claim 45 , wherein the signal processing means utilizes predetermined algorithms including adjustment of detector signals according to weighting factors.  
     
     
         61 . A method for estimating the concentration of an analyte in a biological environment, the method comprising reading a primary composite signal indicative of the analyte concentration from a display in communication with signal processing means in a device according to  claim 29 .  
     
     
         62 . The method according to  claim 61 , wherein the device is implanted in a human tissue.  
     
     
         63 . A method for calibrating the device of  claim 45 , the method comprising adjusting one or more detector signals obtained from the device to zero in the absence of external stimuli.  
     
     
         64 . A method for calibrating the device of  claim 45 , the method comprising adjusting one or more detector signals obtained from the device to reflect the signal expected in response to a known stimulus.