Methods and kits for assays of rapid screening of diabetes

Abstract

The invention provides an in vivo screening assay and an in vitro screening assay for rapid screening of diabetes. A method of the invention includes determining a first glucose concentration in an ocular fluid of a patient; administering orally a load of carbohydrate to the patient; determining a second glucose concentration in an ocular fluid of the patient at a period of time of less than 50 minutes after orally administering of the load of carbohydrate; comparing the second glucose concentration with the first glucose concentration to determine if the patient is likely to be a diabetic. The method of the invention is performed by using a kit of the invention. The kit comprises: (1) a glucose-sensing ophthalmic device and instructions for using the glucose-sensing ophthalmic device to screen for diabetes; or (2) two or more tear-collecting devices, and a testing agent composition which specifically reacts with glucose to form a detectable signal. The glucose-sensing ophthalmic device comprises a testing agent composition which specifically and reversibly interacts with glucose to form a detectable optical signal which changes in a concentration-dependent manner.

1 . A method for rapidly screening for diabetes, comprising the steps of: 
 contacting a glucose-sensing ophthalmic device with an ocular fluid, wherein the glucose-sensing ophthalmic device comprises a testing agent composition which specifically and reversibly interacts with glucose to form a detectable signal which changes in a concentration-dependent manner;    determining by means of the glucose-sensing ophthalmic device a first glucose concentration in the ocular fluid;    administering orally a load of carbohydrate to the patient;    at a period of time of less than 50 minutes after orally administering of the load of carbohydrate, determining by means of the glucose-sensing ophthalmic device a second glucose concentration in the ocular fluid; and    comparing the second glucose concentration with the first glucose concentration to determine if the patient is likely to be a diabetic.    
     
     
         2 . A method of  claim 1 , wherein the second glucose concentration is determined about 15 minutes after orally administering of the load of carbohydrate.  
     
     
         3 . A method of  claim 1 , wherein said testing agent composition comprises a receptor that is capable of reversibly binding glucose and has a detectable optical signal that changes in a concentration-dependent manner when the receptor is reversibly bound to glucose, wherein said detectable optical signal results from one or more labels associated with the receptor.  
     
     
         4 . A method of  claim 3 , wherein the detectable optical signal results from a pair of labels associated with the receptor, a first label and a second label, wherein one of the first and second label is a fluorescence energy donor and the other is a fluorescence energy acceptor or a non-fluorescence energy acceptor.  
     
     
         5 . A method of  claim 1 , wherein said testing agent composition comprises a receptor having a first label associated therewith and a competitor having a second label associated therewith, wherein one of the first and second labels is a fluorescent energy donor and the other one is a fluorescent or non-fluorescent energy acceptor.  
     
     
         6 . A method of  claim 1 , wherein said load of carbohydrate is at least 40 grams of carbohydrate.  
     
     
         7 . A method for rapidly screening for diabetes, comprising the steps of: 
 collecting a first tear fluid from a patient using a first tear-collecting device;    assaying a specific amount of the first tear fluid to determine a first glucose concentration;    administering orally a load of carbohydrate to the patient;    collecting a second tear fluid, at a period of time of less than 50 minutes after orally administering of the load of carbohydrate, using a second tear-collecting device;    assaying a specific amount of the second tear fluid to determine a second glucose concentration; and    comparing the second glucose concentration with the first glucose concentration to determine if the patient is likely to be a diabetic.    
     
     
         8 . A method of  claim 7 , wherein said first and second tear collecting devices are selected from the group consisting of capillary tubes, hydrogel strips, and contact lenses.  
     
     
         9 . A method of  claim 7 , wherein at least one of the first and second tear collecting devices is a strip having a first end and a second end, wherein said strip is made of a hydrogel material in substantially dry state and is characterized by having a substantially uniform swelling along the hydrogel strip from the first end to the second end when fully wicked by a tear fluid and by having a correlation between the volume of tear uptake by said strip and the length of a tear-wicked end portion of said strip.  
     
     
         10 . A method of  claim 7 , wherein said load of carbohydrate is at least 40 grams of carbohydrate.  
     
     
         11 . A method of  claim 7 , wherein said second tear fluid is collected at a period of time of at least 15 minutes after orally administering of the load of carbohydrate.  
     
     
         12 . A kit for rapid screening of diabetes, the kit comprising: a glucose-sensing ophthalmic device and instructions for using the glucose-sensing ophthalmic device to screen for diabetes, wherein the glucose-sensing ophthalmic device comprises a testing agent composition which specifically and reversibly interacts with glucose to form a detectable optical signal which changes in a concentration-dependent manner.  
     
     
         13 . A kit of  claim 12 , wherein said testing agent composition comprises a receptor that is capable of reversibly binding glucose and has a detectable optical signal that changes in a concentration-dependent manner when the receptor is reversibly bound to glucose, wherein said detectable optical signal results from one or more labels associated with the receptor.  
     
     
         14 . A kit of  claim 13 , wherein the detectable optical signal results from a pair of labels associated with the receptor, a first label and a second label, wherein one of the first and second label is a fluorescence energy donor and the other is a fluorescence energy acceptor or a non-fluorescence energy acceptor.  
     
     
         15 . A kit of  claim 14 , wherein said receptor is selected from the group consisting of GGBP, concanavalin A, inactivated glucose oxidase, inactivated glucose dehydrogenase, and boronic acid.  
     
     
         16 . A kit of  claim 14 , wherein said fluorescent energy donor is selected from the group consisting of xanthene-type dyes, fluorescein-type dyes, rhodamine-type dyes, cyanine-type dyes, phycobiliproteins.  
     
     
         17 . A kit of  claim 12 , wherein said testing agent composition comprises a receptor having a first label associated therewith and a competitor having a second label associated therewith, wherein one of the first and second labels is a fluorescent energy donor and the other one is a fluorescent or non-fluorescent energy acceptor.  
     
     
         18 . A kit of  claim 12 , wherein the ophthalmic device can comprise a glucose-sensing LbL coating which is not covalently attached to the core material of the ophthalmic device, wherein the glucose-sensing LbL coating comprises the testing agent composition.  
     
     
         19 . A kit of  claim 18 , wherein the glucose-sensing LbL coating comprises one or more layers of a vesicle with a charged surface and with a receptor or a competitor entrapped therein, wherein the receptor has a first label associated therewith and the competitor has a second label associated therewith, wherein one of the first and second labels is a fluorescent energy donor and the other one is a fluorescent or non-fluorescent energy acceptor.  
     
     
         20 . A kit of  claim 18 , wherein the glucose-sensing LbL coating comprises one or more layers of a vesicle with a charged surface and with a receptor entrapped therein, wherein the receptor is capable of reversibly binding glucose and has a detectable optical signal that changes in a concentration-dependent manner when the receptor is reversibly bound to glucose, wherein said detectable optical signal results from one or more labels associated with the receptor.  
     
     
         21 . A kit of  claim 20 , wherein the detectable optical signal results from a pair of labels associated with the receptor, a first label and a second label, wherein one of the first and second label is a fluorescence energy donor and the other is a fluorescence energy acceptor or a non-fluorescence energy acceptor.  
     
     
         22 . A kit for rapid screening of diabetes, the kit comprising: two or more tear-collecting devices, and a testing agent composition which specifically reacts with glucose to form a detectable signal.  
     
     
         23 . A kit of  claim 22 , wherein said two or more tear-collecting devices are selected from the group consisting of a hydrogel strip, a capillary tube, and a soft-hydrogel contact lens.  
     
     
         24 . A kit of  claim 23 , wherein said two or more tear-collecting devices are hydrogel strips, wherein each of said strips has a first end and an opposite second end, wherein each of said strips is made of a hydrogel material in substantially dry state and is characterized by having a substantially uniform swelling along that hydrogel strip from the first end to the second end when fully wicked by a tear fluid and by having a correlation between the volume of tear uptake by that strip and the length of a tear-wicked end portion of that strip.  
     
     
         25 . A kit of  claim 24 , wherein said hydrogel material is selected from the group consisting of poly(vinyl alcohol), modified polyvinylalcohol, poly(hydroxyethyl methacrylate), poly(vinyl pyrrolidone), poly(vinyl alcohol) with polycarboxylic acids, polyethylene glycol, polyacrylamide, polymethacrylamide, silicone-containing hydrogels, polyurethane, polyurea, and mixtures thereof.  
     
     
         26 . A kit of  claim 24 , wherein said defined correlation between the volume of tear uptake and the length of the tear-wicked end portion is a substantially linear relationship.  
     
     
         27 . A kit of  claim 24 , wherein each of said strips has noticeable marks thereon, wherein each of the marks indicates a volume of the tear fluid absorbed by the end portion up to that mark of that strip.  
     
     
         28 . A kit of  claim 22 , wherein said testing agent composition comprises a receptor that is capable of reversibly binding glucose and has a detectable optical signal that changes in a concentration-dependent manner when the receptor is reversibly bound to glucose, wherein said detectable optical signal results from one or more labels associated with the receptor.  
     
     
         29 . A kit of  claim 28 , wherein said testing agent composition comprises a receptor that is capable of reversibly binding glucose and has a detectable optical signal that changes in a concentration-dependent manner when the receptor is reversibly bound to glucose, wherein said detectable optical signal results from a pair of labels, a first label and a second label, associated with the receptor, wherein one of the first and second label is a fluorescence energy donor and the other is a fluorescence energy acceptor or a non-fluorescence energy acceptor.  
     
     
         30 . A kit of  claim 22 , wherein said testing agent composition comprises a receptor having a first label associated therewith and a competitor having a second label associated therewith, wherein one of the first and second labels is a fluorescent energy donor and the other one is a fluorescent or non-fluorescent energy acceptor.