Ocular analyte sensor

Abstract

An ophthalmic lens comprising a receptor moiety can be used to determine the amount of an analyte in an ocular fluid. The receptor moiety can bind either a specific analyte or a detectably labeled competitor moiety. The amount of detectably labeled competitor moiety which is displaced from the receptor moiety by the analyte is measured and provides a means of determining analyte concentration in an ocular fluid, such as tears, aqueous humor, or interstitial fluid. The concentration of the analyte in the ocular fluid, in turn, indicates the concentration of the analyte in a fluid or tissue sample of the body, such as blood or intracellular fluid.

1 . An ophthalmic lens for detecting glucose in an ocular fluid, comprising:  
       a receptor moiety layer, wherein receptor moieties in the receptor moiety layer comprises glucose oxidase molecules comprising glucose/competitor moiety binding sites;  
       a first and a second polyelectrolyte layer;  
       a competitor moiety layer, and  
       detectable labels which are associated with the receptor moieties or the competitor moieties.  
     
     
         2 . An ophthalmic lens of  claim 1 , wherein the competitor moieties are selected from the group consisting of 2-deoxy-D-glucose, D-mannose and D-galactose.  
     
     
         3 . An ophthalmic lens of  claim 2 , wherein the competitor is tethered to a polymer meshwork, wherein pores of the polymer meshwork (a) permit glucose to bind reversibly to the glucose/competitor moiety binding site and (b) prevent the glucose oxidase from diffusing out of the ophthalmic lens.  
     
     
         4 . An ophthalmic lens of  claim 3 , wherein the detectable labels are fluorescent labels.  
     
     
         5 . An ophthalmic lens of  claim 4 , wherein the fluorescent labels are selected from the group consisting of fluorescein, indocyanine green, malachite green, rhodamine, Alexa Fluor® dyes, Oregon Green® dyes, BODIPY fluorophores, cyanine dyes, and phycobiliproteins.  
     
     
         6 . A glucose sensor system, comprising: 
 (a) an ophthalmic lens for detecting glucose in an ocular fluid, comprising: 
 (i) glucose oxidase molecules each of which comprises a glucose/competitor moiety binding site; and  
 (ii) a competitor moiety comprising a detectable label; and  
   (b) a detector configured to detect the detectable label.    
     
     
         7 . A glucose sensor system of  claim 6 , wherein the competitor moiety is selected from the group consisting of 2-deoxy-D-glucose, D-mannose and D-galactose.  
     
     
         8 . A glucose sensor system of  claim 7 , wherein the competitor is tethered to a polymer meshwork, wherein pores of the polymer meshwork (a) permit glucose to bind reversibly to the glucose/competitor moiety binding site and (b) prevent the glucose oxidase from diffusing out of the ophthalmic lens.  
     
     
         9 . A glucose sensor system of  claim 8 , wherein the detector includes a fluorophotometer.  
     
     
         10 . A glucose sensor system of  claim 9 , further comprising a transmitter coupled to the detector and configured to transmit to a pump a signal indicating whether the detectable label is detected by the detector, wherein the pump is configured to vary glucose concentration in a body fluid or tissue.  
     
     
         11 . A glucose sensor system of  claim 10 , wherein the transmitter is contained in a personal accessory.  
     
     
         12 . A glucose sensor system of  claim 11 , further comprising the pump.  
     
     
         13 . A glucose sensor system of  claim 12 , wherein the transmitter is further configured to transmit the signal to the pump wirelessly.  
     
     
         14 . A glucose sensor system of  claim 13 , wherein the pump is an insulin pump.  
     
     
         15 . A glucose sensor system of  claim 14 , wherein the ophthalmic lens is selected from the group consisting of a contact lens, an intraocular lens, a subconjunctival lens, and an intracorneal lens.  
     
     
         16 . A method for measuring glucose concentration in an ocular fluid, comprising the steps of: 
 (a) contacting the ocular fluid with an ophthalmic lens, wherein the ophthalmic lens comprises: 
 (i) glucose oxidase molecules each of which comprises a glucose/competitor moiety binding site; and  
 (ii) a competitor moiety which comprises a detectable label; and  
   (b) detecting the detectable label, wherein the amount of detectable label detected indicates the glucose concentration in the ocular fluid.    
     
     
         17 . The method of  claim 16 , wherein the competitor moiety is selected from the group consisting of 2-deoxy-D-glucose, D-mannose and D-galactose.  
     
     
         18 . The method of  claim 17 , wherein the competitor is tethered to a polymer meshwork, wherein pores of the polymer meshwork (a) permit glucose to bind reversibly to the glucose/competitor moiety binding site and (b) prevent the glucose oxidase from diffusing out of the ophthalmic lens.  
     
     
         19 . The method of  claim 18 , wherein the detectable label is a fluorescent label.  
     
     
         20 . The method of  claim 19 , wherein the ophthalmic lens is selected from the group consisting of a contact lens, an intraocular lens, a subconjunctival lens, and an intracorneal lens.  
     
     
         21 . A method for varying glucose concentration in an ocular fluid, comprising the steps of: 
 (a) contacting the ocular fluid with an ophthalmic lens, wherein the ophthalmic lens comprises: 
 (i) a competitor moiety which comprises a detectable label; and  
 (ii) glucose oxidase molecules each of which comprises a glucose/competitor moiety binding site;  
   (b) detecting the detectable label, wherein the amount of detectable label detected indicates the glucose concentration in a body tissue or fluid;    (c) transmitting a signal indicating the glucose concentration in the ocular fluid to a pump configured to vary the glucose concentration in the body tissue or fluid; and    (d) providing a regulator moiety via the pump to the body tissue or fluid, whereby the glucose concentration in the body tissue or fluid is varied.    
     
     
         22 . The method of  claim 21 , wherein the competitor moiety is selected from the group consisting of 2-deoxy-D-glucose, D-mannose and D-galactose.  
     
     
         23 . The method of  claim 22 , wherein the competitor is tethered to a polymer meshwork, wherein pores of the polymer meshwork (a) permit glucose to bind reversibly to the glucose/competitor moiety binding site and (b) prevent the glucose oxidase from diffusing out of the ophthalmic lens.  
     
     
         24 . The method of  claim 23 , wherein the detectable label is a fluorescent label.  
     
     
         25 . The method of  claim 24 , wherein the regulator moiety is insulin.  
     
     
         26 . The method of  claim 25 , wherein the detectable label is detected by a fluorophotometer.  
     
     
         27 . The method of  claim 26 , wherein the fluorophotometer is contained in a personal accessory.  
     
     
         28 . The method of  claim 27 , wherein the ophthalmic lens is selected from the group consisting of a contact lens, an intraocular lens, a subconjunctival lens, and an intracorneal lens.